Evaluation of Inflammatory Cells (Tumor Infiltrating Lymphocytes) in Solid Tumors
Authors:
P. Dundr 1; K. Němejcová 1; M. Bártů 1; R. Matěj 1,2; Z. Rohan 1,2; I. Tichá 1
Authors place of work:
Ústav patologie 1. LF UK a VFN v Praze
1; Oddělení patologie a molekulární medicíny, Thomayerova nemocnice, Praha
2
Published in the journal:
Klin Onkol 2017; 30(Supplementum3): 10-21
Category:
Review
doi:
https://doi.org/10.14735/amko20173S10
Summary
Background:
The tumor microenvironment plays an important role in tumorigenesis and the tumor-host relationship. An important part of the tumor microenvironment is inflammatory infiltration. Its evaluation in solid tumors has prognostic meaning and appears also to be predictive of outcome, which is particularly important for predicting responses to immune checkpoint inhibitors. However, the methodology used to assess inflammatory infiltration is problematic, because it has been standardized only for certain types of tumors.
Objective:
The present study provides an overview of current issues related to the evaluation of inflammatory cells (tumor infiltrating lymphocytes) in solid tumors, specifically in tumors of the breast, lung, head and neck, gastrointestinal tract, female genital tract, urogenital tract, brain, malignant mesothelioma, and malignant melanoma. Various methodologies for evaluation are mentioned, including the efforts that are being made to standardize these methodologies and the importance of immunophenotyping inflammatory infiltrates. With regard to clinical meaning, prognostic and predictive significance are also discussed.
Conclusion:
The evaluation of TILs in solid tumors often has predictive value; however, the results have been equivocal. There is also ambiguity about the predictive use of this marker. Despite all the methodological developments, which have resulted in the implementation of complicated technologies (image analysis, multiplex fluorescence immunohistochemistry, and mass spectrometry) for the evaluation of the various aspects of inflammatory infiltrates present in tumors, including their functional characteristics, there is still a need for standardization and development of inexpensive and universally available methodologies to enable the wide use of TIL evaluations in clinical settings. The recently proposed unified methodology may be used in all solid tumors and could help resolve one of the main limitations of the routine use of TIL, i.e., the inconsistent approach to assessment.
Key words:
solid tumors – tumor-infiltratig lymphocytes – inflammatory cells
This work was supported by program of the Czech Ministry of Health No. RVO-VFN 64165 and AZV project No. 16-30954A, Charles University and OPPK (CZ.2.16/3.1.00/24509).
The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study.
The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers.
Submitted:
24. 9. 2017
Accepted:
3. 10. 2017
Zdroje
1. Hendry S, Salgado R, Gevaert T et al. Assessing Tumor-infiltrating Lymphocytes in Solid Tumors: A Practical Review for Pathologists and Proposal for a Standardized Method From the International Immunooncology Biomarkers Working Group: Part 1: Assessing the Host Immune Response, TILs in Invasive Breast Carcinoma and Ductal Carcinoma In Situ, Metastatic Tumor Deposits and Areas for Further Research. Adv Anat Pathol 2017; 24 (5): 235–251. doi: 10.1097/PAP.0000000000000162.
2. Hendry S, Salgado R, Gevaert T et al. Assessing Tumor-Infiltrating Lymphocytes in Solid Tumors: A Practical Review for Pathologists and Proposal for a Standardized Method from the International Immuno-Oncology Biomarkers Working Group: Part 2: TILs in Melanoma, Gastrointestinal Tract Carcinomas, Non-Small Cell Lung Carcinoma and Mesothelioma, Endometrial and Ovarian Carcinomas, Squamous Cell Carcinoma of the Head and Neck, Genitourinary Carcinomas, and Primary Brain Tumors. Adv Anat Pathol 2017. doi: 10.1097/PAP.0000000000000161.
3. Day CL Jr, Sober AJ, Kopf AW et al. A prognostic model for clinical stage I melanoma of the trunk. Location near the midline is not an independent risk factor for recurrent disease. Am J Surg 1981; 142 (2): 247–251. doi: 10.1016/0002-9610 (81) 90286-5.
4. Clark WH Jr, Elder DE, Guerry D et al. Model predicting survival in stage I melanoma based on tumor progression. J Natl Cancer Inst 1989; 81 (24): 1893–1904.
5. Azimi F, Scolyer RA, Rumcheva P et al. Tumor-infiltrating lymphocyte grade is an independent predictor of sentinel lymph node status and survival in patients with cutaneous melanoma. J Clin Oncol 2012; 30 (21): 2678–2683. doi: 10.1200/JCO.2011.37.8539.
6. Park CK, Kim SK. Clinicopathological significance of intratumoral and peritumoral lymphocytes and lymphocyte score based on the histologic subtypes of cutaneous melanoma. Oncotarget 2017; 8 (9): 14759–14769. doi: 10.18632/oncotarget.14736.
7. Saldanha G, Flatman K, Teo KW et al. A Novel Numerical Scoring System for Melanoma Tumor-infiltrating Lymphocytes Has Better Prognostic Value Than Standard Scoring. Am J Surg Pathol 2017; 41 (7): 906–914. doi: 10.1097/PAS.0000000000000848.
8. Thomas NE, Busam KJ, From L et al. Tumor-infiltrating lymphocyte grade in primary melanomas is independently associated with melanoma-specific survival in the population-based genes, environment and melanoma study. J Clin Oncol 2013; 31 (33): 4252–4259. doi: 10.1200/JCO.2013.51.3002.
9. Clemente CG, Mihm MC Jr, Bufalino R et al. Prognostic value of tumor infiltrating lymphocytes in the vertical growth phase of primary cutaneous melanoma. Cancer 1996; 77 (7): 1303–1310. doi: 10.1002/ (SICI) 1097-0142 (19960401) 77: 7<1303:: AID-CNCR12>3.0.CO; 2-5.
10. Burton AL, Roach BA, Mays MP et al. Prognostic significance of tumor infiltrating lymphocytes in melanoma. Am Surg 2011; 77 (2): 188–192.
11. Cancer Genome Atlas N. Genomic Classification of Cutaneous Melanoma. Cell 2015; 161 (7): 1681–1696.
12. Tumeh PC, Harview CL, Yearley JH et al. PD-1 blockade induces responses by inhibiting adaptive immune resistance. Nature 2014; 515 (7528): 568–571. doi: 10.1038/nature13954.
13. Galon J, Costes A, Sanchez-Cabo F et al. Type, density, and location of immune cells within human colorectal tumors predict clinical outcome. Science 2006; 313 (5795): 1960–1964. doi: 10.1126/science.1129139.
14. Mlecnik B, Tosolini M, Kirilovsky A et al. Histopathologic-based prognostic factors of colorectal cancers are associated with the state of the local immune reaction. J Clin Oncol 2011; 29 (6): 610–618. doi: 10.1200/JCO.2010.30.5425.
15. Baxevanis CN, Papamichail M, Perez SA. Immune classification of colorectal cancer patients: impressive but how complete? Expert Opin Biol Ther 2013; 13 (4): 517–526. doi: 10.1517/14712598.2013.751971.
16. Dahlin AM, Henriksson ML, Van Guelpen B et al. Colorectal cancer prognosis depends on T-cell infiltration and molecular characteristics of the tumor. Mod Pathol 2011; 24 (5): 671–682. doi: 10.1038/modpathol.2010.234.
17. Zavadova E, Spacek J, Vocka M et al. Immunoscore and Its Predictive Value for Colorectal Cancer. Klin Onkol 2015; 28 (Suppl 4): 82–85. doi: 10.14735/amko20154S82.
18. Pages F, Kirilovsky A, Mlecnik B et al. In situ cytotoxic and memory T cells predict outcome in patients with early-stage colorectal cancer. J Clin Oncol 2009; 27 (35): 5944–5951. doi: 10.1200/JCO.2008.19.6147.
19. Broussard EK, Disis ML. TNM staging in colorectal cancer: T is for T cell and M is for memory. J Clin Oncol 2011; 29 (6): 601–603. doi: 10.1200/JCO.2010.32.9078.
20. Anitei MG, Zeitoun G, Mlecnik B et al. Prognostic and predictive values of the immunoscore in patients with rectal cancer. Clin Cancer Res 2014; 20 (7): 1891–1899. doi: 10.1158/1078-0432.CCR-13-2830.
21. Koelzer VH, Lugli A, Dawson H et al. CD8/CD45RO T-cell infiltration in endoscopic biopsies of colorectal cancer predicts nodal metastasis and survival. J Transl Med 2014; 12: 81. doi: 10.1186/1479-5876-12-81.
22. Morris M, Platell C, Iacopetta B. Tumor-infiltrating lymphocytes and perforation in colon cancer predict positive response to 5-fluorouracil chemotherapy. Clin Cancer Res 2008; 14 (5): 1413–1417. doi: 10.1158/1078-0432.CCR-07-1994.
23. Halama N, Michel S, Kloor M et al. Localization and density of immune cells in the invasive margin of human colorectal cancer liver metastases are prognostic for response to chemotherapy. Cancer Res 2011; 71 (17): 5670–5607. doi: 10.1158/0008-5472.CAN-11-0268.
24. Galon J, Mlecnik B, Bindea G et al. Towards the introduction of the ‚Immunoscore‘ in the classification of malignant tumours. J Pathol 2014; 232 (2): 199–209. doi: 10.1002/path.4287.
25. Lee JY, Son T, Cheong JH et al. Association between Chemotherapy-Response Assays and Subsets of Tumor-Infiltrating Lymphocytes in Gastric Cancer: A Pilot Study. J Gastric Cancer 2015; 15 (4): 223–230. doi: 10.5230/jgc.2015.15.4.223.
26. Liu K, Yang K, Wu B et al. Tumor-Infiltrating Immune Cells Are Associated With Prognosis of Gastric Cancer. Medicine (Baltimore) 2015; 94 (39): e1631. doi: 10.1097/MD.0000000000001631.
27. Haas M, Dimmler A, Hohenberger W et al. Stromal regulatory T-cells are associated with a favourable prognosis in gastric cancer of the cardia. BMC Gastroenterol 2009; 9: 65. doi: 10.1186/1471-230X-9-65.
28. Haas M, Buttner M, Rau TT et al. Inflammation in gastric adenocarcinoma of the cardia: how do EBV infection, Her2 amplification and cancer progression influence tumor-infiltrating lymphocytes? Virchows Arch 2011; 458 (4): 403–411. doi: 10.1007/s00428-011-1058-1.
29. Kim SY, Park C, Kim HJ et al. Deregulation of immune response genes in patients with Epstein-Barr virus-associated gastric cancer and outcomes. Gastroenterology 2015; 148 (1): 137–147. e9. doi: 10.1053/j.gastro.2014.09.020.
30. Dai C, Geng R, Wang C et al. Concordance of immune checkpoints within tumor immune contexture and their prognostic significance in gastric cancer. Mol Oncol 2016; 10 (10): 1551–1558. doi: 10.1016/j.molonc.2016.09. 004.
31. Chiaravalli AM, Feltri M, Bertolini V et al. Intratumour T cells, their activation status and survival in gastric carcinomas characterised for microsatellite instability and Epstein-Barr virus infection. Virchows Arch 2006; 448 (3): 344–353. doi: 10.1007/s00428-005-0066-4.
32. Solinas C, Pusole G, Demurtas L et al. Tumor infiltrating lymphocytes in gastrointestinal tumors: Controversies and future clinical implications. Crit Rev Oncol Hematol 2017; 110: 106–116. doi: 10.1016/j.critrevonc.2016.11.016.
33. Wang M, Busuttil RA, Pattison S et al. Immunological battlefield in gastric cancer and role of immunothe-rapies. World J Gastroenterol 2016; 22 (28): 6373–6384. doi: 10.3748/wjg.v22.i28.6373.
34. Kang BW, Seo AN, Yoon S et al. Prognostic value of tumor-infiltrating lymphocytes in Epstein-Barr virus-associated gastric cancer. Ann Oncol 2016; 27 (3): 494–501. doi: 10.1093/annonc/mdv610.
35. Erkan M, Hausmann S, Michalski CW et al. The role of stroma in pancreatic cancer: diagnostic and therapeutic implications. Nat Rev Gastroenterol Hepatol 2012; 9 (8): 454–467. doi: 10.1038/nrgastro.2012.115.
36. Nielsen MF, Mortensen MB, Detlefsen S. Key players in pancreatic cancer-stroma interaction: Cancer-associated fibroblasts, endothelial and inflammatory cells. World J Gastroenterol 2016; 22 (9): 2678–2700. doi: 10.3748/wjg.v22.i9.2678.
37. Ino Y, Yamazaki-Itoh R, Shimada K et al. Immune cell infiltration as an indicator of the immune microenvironment of pancreatic cancer. Br J Cancer 2013; 108 (4): 914–923. doi: 10.1038/bjc.2013.32.
38. Hiraoka N, Ino Y, Yamazaki-Itoh R et al. Intratumoral tertiary lymphoid organ is a favourable prognosticator in patients with pancreatic cancer. Br J Cancer 2015; 112 (11): 1782–1790. doi: 10.1038/bjc.2015.145.
39. Gabrielson A, Wu Y, Wang H et al. Intratumoral CD3 and CD8 T-cell Densities Associated with Relapse-Free Survival in HCC. Cancer Immunol Res 2016; 4 (5): 419–430. doi: 10.1158/2326-6066.CIR-15-0110.
40. Chew V, Tow C, Teo M et al. Inflammatory tumour microenvironment is associated with superior survival in hepatocellular carcinoma patients. J Hepatol 2010; 52 (3): 370–379. doi: 10.1016/j.jhep.2009.07.013.
41. Sideras K, Biermann K, Verheij J et al. PD-L1, Galectin-9 and CD8+ tumor-infiltrating lymphocytes are associated with survival in hepatocellular carcinoma. Oncoimmunology 2017; 6 (2): e1273309. doi: 10.1080/2162402X.2016.1273309.
42. Chang H, Jung W, Kim A et al. Expression and prognostic significance of programmed death protein 1 and programmed death ligand-1, and cytotoxic T lymphocyte-associated molecule-4 in hepatocellular carcinoma. APMIS 2017; 125 (8): 690–608. doi: 10.1111/apm.12703.
43. Chen KJ, Zhou L, Xie HY et al. Intratumoral regulatory T cells alone or in combination with cytotoxic T cells predict prognosis of hepatocellular carcinoma after resection. Med Oncol 2012; 29 (3): 1817–1826. doi: 10.1007/s12032-011-0006-x.
44. Garnelo M, Tan A, Her Z et al. Interaction between tumour-infiltrating B cells and T cells controls the progression of hepatocellular carcinoma. Gut 2017; 66 (2): 342–351. doi: 10.1136/gutjnl-2015-310814.
45. Stanton SE, Adams S, Disis ML. Variation in the Incidence and Magnitude of Tumor-Infiltrating Lymphocytes in Breast Cancer Subtypes: A Systematic Review. JAMA Oncol 2016; 2 (10): 1354–1360. doi: 10.1001/jamaoncol.2016.1061.
46. Savas P, Salgado R, Denkert C et al. Clinical relevance of host immunity in breast cancer: from TILs to the clinic. Nat Rev Clin Oncol 2016; 13 (4): 228–241. doi: 10.1038/nrclinonc.2015.215.
47. Mao Y, Qu Q, Chen X et al. The Prognostic Value of Tumor-Infiltrating Lymphocytes in Breast Cancer: A Systematic Review and Meta-Analysis. PLoS One 2016; 11 (4): e0152500. doi: 10.1371/journal.pone.0152500.
48. Wang Q, Zhao L, Yang X et al. Antibody 1A4 with routine immunohistochemistry demonstrates high sensitivity for ALK rearrangement screening of Chinese lung adenocarcinoma patients: A single-center large-scale study. Lung Cancer 2016; 95: 39–43. doi: 10.1016/j.lungcan.2016.02.014.
49. Denkert C, Loibl S, Noske A et al. Tumor-associated lymphocytes as an independent predictor of response to neoadjuvant chemotherapy in breast cancer. J Clin Oncol 2010; 28 (1): 105–113. doi: 10.1200/JCO.2009.23. 7370.
50. Loi S, Michiels S, Salgado R et al. Tumor infiltrating lymphocytes are prognostic in triple negative breast cancer and predictive for trastuzumab benefit in early breast cancer: results from the FinHER trial. Ann Oncol 2014; 25 (8): 1544–1550. doi: 10.1093/annonc/mdu112.
51. Loi S, Sirtaine N, Piette F et al. Prognostic and predictive value of tumor-infiltrating lymphocytes in a phase III randomized adjuvant breast cancer trial in node-positive breast cancer comparing the addition of docetaxel to doxorubicin with doxorubicin-based chemotherapy: BIG 02-98. J Clin Oncol 2013; 31 (7): 860–867. doi: 10.1200/JCO.2011.41.0902.
52. Adams S, Gray RJ, Demaria S et al. Prognostic value of tumor-infiltrating lymphocytes in triple-negative breast cancers from two phase III randomized adjuvant breast cancer trials: ECOG 2197 and ECOG 1199. J Clin Oncol 2014; 32 (27): 2959–2966. doi: 10.1200/JCO.2013.55. 0491.
53. Pruneri G, Gray KP, Vingiani A et al. Tumor-infiltrating lymphocytes (TILs) are a powerful prognostic marker in patients with triple-negative breast cancer enrolled in the IBCSG phase III randomized clinical trial 22-00. Breast Cancer Res Treat 2016; 158 (2): 323–231. doi: 10.1007/s10549-016-3863-3.
54. Dieci MV, Criscitiello C, Goubar A et al. Prognostic value of tumor-infiltrating lymphocytes on residual disease after primary chemotherapy for triple-negative breast cancer: a retrospective multicenter study. Ann Oncol 2014; 25 (3): 611–618. doi: 10.1093/annonc/mdt556.
55. Ibrahim EM, Al-Foheidi ME, Al-Mansour MM et al. The prognostic value of tumor-infiltrating lymphocytes in triple-negative breast cancer: a meta-analysis. Breast Cancer Res Treat 2014; 148 (3): 467–476. doi: 10.1007/s10549-014-3185-2.
56. Wang ZQ, Milne K, Derocher H et al. CD103 and Intratumoral Immune Response in Breast Cancer. Clin Cancer Res 2016; 22 (24): 6290–6297. doi: 10.1158/1078-0432.CCR-16-0732.
57. Shou J, Zhang Z, Lai Y et al. Worse outcome in breast cancer with higher tumor-infiltrating FOXP3+ Tregs: a systematic review and meta-analysis. BMC Cancer 2016; 16: 687. doi: 10.1186/s12885-016-2732-0.
58. West NR, Kost SE, Martin SD et al. Tumour-infiltrating FOXP3 (+) lymphocytes are associated with cytotoxic immune responses and good clinical outcome in oestrogen receptor-negative breast cancer. Br J Cancer 2013; 108 (1): 155–162. doi: 10.1038/bjc.2012.524.
59. Liu S, Foulkes WD, Leung S et al. Prognostic significance of FOXP3+ tumor-infiltrating lymphocytes in breast cancer depends on estrogen receptor and human epidermal growth factor receptor-2 expression status and concurrent cytotoxic T-cell infiltration. Breast Cancer Res 2014; 16 (5): 432. doi: 10.1186/s13058-014-0432-8.
60. Generali D, Bates G, Berruti A et al. Immunomodulation of FOXP3+ regulatory T cells by the aromatase inhibitor letrozole in breast cancer patients. Clin Cancer Res 2009; 15 (3): 1046–1051. doi: 10.1158/1078-0432.CCR-08-1507.
61. Bertucci F, Goncalves A. Immunotherapy in Breast Cancer: the Emerging Role of PD-1 and PD-L1. Curr Oncol Rep 2017; 19 (10): 64. doi: 10.1007/s11912-017-0627-0.
62. West NR, Milne K, Truong PT et al. Tumor-infiltrating lymphocytes predict response to anthracycline-based chemotherapy in estrogen receptor-negative breast cancer. Breast Cancer Res 2011; 13 (6): R126. doi: 10.1186/bcr3072.
63. Ali HR, Provenzano E, Dawson SJ et al. Association between CD8+ T-cell infiltration and breast cancer survival in 12,439 patients. Ann Oncol 2014; 25 (8): 1536–1543. doi: 10.1093/annonc/mdu191.
64. Salgado R, Denkert C, Demaria S et al. The evaluation of tumor-infiltrating lymphocytes (TILs) in breast cancer: recommendations by an International TILs Working Group 2014. Ann Oncol 2015; 26 (2): 259–271. doi: 10.1093/annonc/mdu450.
65. Campbell MJ, Baehner F, O‘Meara T et al. Characterizing the immune microenvironment in high-risk ductal carcinoma in situ of the breast. Breast Cancer Res Treat 2017; 161 (1): 17–28. doi: 10.1007/s10549-016-4036-0.
66. Zhang L, Conejo-Garcia JR, Katsaros D et al. Intratumoral T cells, recurrence, and survival in epithelial ovarian cancer. N Engl J Med 2003; 348 (3): 203–213. doi: 10.1056/NEJMoa020177.
67. Hwang WT, Adams SF, Tahirovic E et al. Prognostic significance of tumor-infiltrating T cells in ovarian cancer: a meta-analysis. Gynecol Oncol 2012; 124 (2): 192–198. doi: 10.1016/j.ygyno.2011.09.039.
68. Preston CC, Maurer MJ, Oberg AL et al. The ratios of CD8+ T cells to CD4+CD25+ FOXP3+ and FOXP3-T cells correlate with poor clinical outcome in human serous ovarian cancer. PLoS One 2013; 8 (11): e80063. doi: 10.1371/journal.pone.0080063.
69. Shah CA, Allison KH, Garcia RL et al. Intratumoral T cells, tumor-associated macrophages, and regulatory T cells: association with p53 mutations, circulating tumor DNA and survival in women with ovarian cancer. Gynecol Oncol 2008; 109 (2): 215–219. doi: 10.1016/j.ygyno.2008.01.010.
70. Bohm S, Montfort A, Pearce OM et al. Neoadjuvant Chemotherapy Modulates the Immune Microenvironment in Metastases of Tubo-Ovarian High-Grade Serous Carcinoma. Clin Cancer Res 2016; 22 (12): 3025–3036. doi: 10.1158/1078-0432.CCR-15-2657.
71. Mesnage SJL, Auguste A, Genestie C et al. Neoadjuvant chemotherapy (NACT) increases immune infiltration and programmed death-ligand 1 (PD-L1) expression in epithelial ovarian cancer (EOC). Ann Oncol 2017; 28 (3): 651–657. doi: 10.1093/annonc/mdw625.
72. Lo CS, Sanii S, Kroeger DR et al. Neoadjuvant Chemotherapy of Ovarian Cancer Results in Three Patterns of Tumor-Infiltrating Lymphocyte Response with Distinct Implications for Immunotherapy. Clin Cancer Res 2017; 23 (4): 925–934. doi: 10.1158/1078-0432.CCR-16-1433.
73. Cancer Genome Atlas Research N. Integrated genomic analyses of ovarian carcinoma. Nature 2011; 474 (7353): 609–615. doi: 10.1038/nature10166.
74. George J, Alsop K, Etemadmoghadam D et al. Nonequivalent gene expression and copy number alterations in high-grade serous ovarian cancers with BRCA1 and BRCA2 mutations. Clin Cancer Res 2013; 19 (13): 3474–3484. doi: 10.1158/1078-0432.CCR-13-0066.
75. Clarke B, Tinker AV, Lee CH et al. Intraepithelial T cells and prognosis in ovarian carcinoma: novel associations with stage, tumor type, and BRCA1 loss. Mod Pathol 2009; 22 (3): 393–402. doi: 10.1038/modpathol.2008.191.
76. Soslow RA, Han G, Park KJ et al. Morphologic patterns associated with BRCA1 and BRCA2 genotype in ovarian carcinoma. Mod Pathol 2012; 25 (4): 625–636. doi: 10.1038/modpathol.2011.183.
77. Stumpf M, Hasenburg A, Riener MO et al. Intraepithelial CD8-positive T lymphocytes predict survival for patients with serous stage III ovarian carcinomas: relevance of clonal selection of T lymphocytes. Br J Cancer 2009; 101 (9): 1513–1521. doi: 10.1038/sj.bjc.6605274.
78. Darb-Esfahani S, Kunze CA et al. Prognostic impact of programmed cell death-1 (PD-1) and PD-ligand 1 (PD-L1) expression in cancer cells and tumor-infiltrating lymphocytes in ovarian high grade serous carcinoma. Oncotarget 2016; 7 (2): 1486–1499. doi: 10.18632/oncotarget. 6429.
79. Hagemann AR, Hagemann IS, Cadungog M et al. Tissue-based immune monitoring II: multiple tumor sites reveal immunologic homogeneity in serous ovarian carcinoma. Cancer Biol Ther 2011; 12 (4): 367–377.
80. Barnett JC, Bean SM, Whitaker RS et al. Ovarian cancer tumor infiltrating T-regulatory (T (reg)) cells are associated with a metastatic phenotype. Gynecol Oncol 2010; 116 (3): 556–562. doi: 10.1016/j.ygyno.2009.11.020.
81. Milne K, Kobel M, Kalloger SE et al. Systematic analysis of immune infiltrates in high-grade serous ovarian cancer reveals CD20, FoxP3 and TIA-1 as positive prognostic factors. PLoS One 2009; 4 (7): e6412. doi: 10.1371/journal.pone.0006412.
82. Hermans C, Anz D, Engel J et al. Analysis of FoxP3+ T-regulatory cells and CD8+ T-cells in ovarian carcinoma: location and tumor infiltration patterns are key prognostic markers. PLoS One 2014; 9 (11): e111757. doi: 10.1371/journal.pone.0111757.
83. Nielsen JS, Sahota RA, Milne K et al. CD20+ tumor-infiltrating lymphocytes have an atypical CD27-memory phenotype and together with CD8+ T cells promote favorable prognosis in ovarian cancer. Clin Cancer Res 2012; 18 (12): 3281–3292. doi: 10.1158/1078-0432.CCR-12-0234.
84. Kroeger DR, Milne K, Nelson BH. Tumor-Infiltrating Plasma Cells Are Associated with Tertiary Lymphoid Structures, Cytolytic T-Cell Responses, and Superior Prognosis in Ovarian Cancer. Clin Cancer Res 2016; 22 (12): 3005–3015. doi: 10.1158/1078-0432.CCR-15-2762.
85. Shia J, Black D, Hummer AJ et al. Routinely assessed morphological features correlate with microsatellite instability status in endometrial cancer. Hum Pathol 2008; 39 (1): 116–125. doi: 10.1016/j.humpath.2007.05.022.
86. Garg K, Leitao MM Jr, Kauff ND et al. Selection of endometrial carcinomas for DNA mismatch repair protein immunohistochemistry using patient age and tumor morphology enhances detection of mismatch repair abnormalities. Am J Surg Pathol 2009; 33 (6): 925–933. doi: 10.1097/PAS.0b013e318197a046.
87. Kandoth C, Schultz N, Cherniack AD et al. Integrated genomic characterization of endometrial carcinoma. Nature 2013; 497 (7447): 67–73. doi: 10.1038/nature12 113.
88. Church DN, Stelloo E, Nout RA et al. Prognostic significance of POLE proofreading mutations in endometrial cancer. J Natl Cancer Inst 2015; 107 (1): 402. doi: 10.1093/jnci/dju402.
89. Cermakova P, Melichar B, Tomsova M et al. Prognostic significance of CD3+ tumor-infiltrating lymphocytes in patients with endometrial carcinoma. Anticancer Res 2014; 34 (10): 5555–5561.
90. de Jong RA, Leffers N, Boezen HM et al. Presence of tumor-infiltrating lymphocytes is an independent prognostic factor in type I and II endometrial cancer. Gynecol Oncol 2009; 114 (1): 105–110. doi: 10.1016/j.ygyno.2009.03.022.
91. Suemori T, Susumu N, Iwata T et al. Intratumoral CD8+ Lymphocyte Infiltration as a Prognostic Factor and Its Relationship With Cyclooxygenase 2 Expression and Microsatellite Instability in Endometrial Cancer. Int J Gynecol Cancer 2015; 25 (7): 1165–1172. doi: 10.1097/IGC.0000000000000482.
92. Howitt BE, Shukla SA, Sholl LM et al. Association of Polymerase e-Mutated and Microsatellite-Instable Endometrial Cancers With Neoantigen Load, Number of Tumor-Infiltrating Lymphocytes, and Expression of PD-1 and PD-L1. JAMA Oncol 2015; 1 (9): 1319–1323. doi: 10.1001/jamaoncol.2015.2151.
93. Le DT, Uram JN, Wang H et al. PD-1 Blockade in Tumors with Mismatch-Repair Deficiency. N Engl J Med 2015; 372 (26): 2509–2520. doi: 10.1056/NEJMoa1500 596.
94. van Gool IC, Eggink FA, Freeman-Mills L et al. POLE Proofreading Mutations Elicit an Antitumor Immune Response in Endometrial Cancer. Clin Cancer Res 2015; 21 (14): 3347–3355. doi: 10.1158/1078-0432.CCR-15-0057.
95. Ino K, Yamamoto E, Shibata K et al. Inverse correlation between tumoral indoleamine 2,3-dioxygenase expression and tumor-infiltrating lymphocytes in endometrial cancer: its association with disease progression and survival. Clin Cancer Res 2008; 14 (8): 2310–2317. doi: 10.1158/1078-0432.CCR-07-4144.
96. Workel HH, Komdeur FL, Wouters MC et al. CD103 defines intraepithelial CD8+ PD1+ tumour-infiltrating lymphocytes of prognostic significance in endometrial adenocarcinoma. Eur J Cancer 2016; 60: 1–11. doi: 10.1016/j.ejca.2016.02.026.
97. Yamagami W, Susumu N, Tanaka H et al. Immunofluorescence-detected infiltration of CD4+FOXP3+ regulatory T cells is relevant to the prognosis of patients with endometrial cancer. Int J Gynecol Cancer 2011; 21 (9): 1628–1634. doi: 10.1097/IGC.0b013e31822c271f.
98. Zeng DQ, Yu YF, Ou QY et al. Prognostic and predictive value of tumor-infiltrating lymphocytes for clinical therapeutic research in patients with non-small cell lung cancer. Oncotarget 2016; 7 (12): 13765–13781. doi: 10.18632/oncotarget.7282.
99. Remark R, Becker C, Gomez JE et al. The non-small cell lung cancer immune contexture. A major determinant of tumor characteristics and patient outcome. Am J Respir Crit Care Med 2015; 191 (4): 377–390. doi: 10.1164/rccm.201409-1671PP.
100. Rehman JA, Han G, Carvajal-Hausdorf DE et al. Quantitative and pathologist-read comparison of the heterogeneity of programmed death-ligand 1 (PD-L1) expression in non-small cell lung cancer. Mod Pathol 2017; 30 (3): 340–349. doi: 10.1038/modpathol.2016. 186.
101. Pichler R, Fritz J, Zavadil C et al. Tumor-infiltrating immune cell subpopulations influence the oncologic outcome after intravesical Bacillus Calmette-Guerin therapy in bladder cancer. Oncotarget 2016; 7 (26): 39916–39930. doi: 10.18632/oncotarget.9537.
102. Horn T, Laus J, Seitz AK et al. The prognostic effect of tumour-infiltrating lymphocytic subpopulations in bladder cancer. World J Urol 2016; 34 (2): 181–187. doi: 10.1007/s00345-015-1615-3.
103. Baras AS, Drake C, Liu JJ et al. The ratio of CD8 to Treg tumor-infiltrating lymphocytes is associated with response to cisplatin-based neoadjuvant chemotherapy in patients with muscle invasive urothelial carcinoma of the bladder. Oncoimmunology 2016; 5 (5): e1134412. doi: 10.1080/2162402X.2015.1134412.
104. Gannon PO, Poisson AO, Delvoye N et al. Characterization of the intra-prostatic immune cell infiltration in androgen-deprived prostate cancer patients. J Immunol Methods 2009; 348 (1–2): 9–17. doi: 10.1016/j.jim.2009.06.004.
105. Geissler K, Fornara P, Lautenschlager C et al. Immune signature of tumor infiltrating immune cells in renal cancer. Oncoimmunology 2015; 4 (1): e985082. doi: 10.4161/2162402X.2014.985082.
106. Baine MK, Turcu G, Zito CR et al. Characterization of tumor infiltrating lymphocytes in paired primary and metastatic renal cell carcinoma specimens. Oncotarget 2015; 6 (28): 24990–5002.
107. Gieryng A, Pszczolkowska D, Walentynowicz KA et al. Immune microenvironment of gliomas. Lab Invest 2017; 97 (5): 498–518. doi: 10.1038/labinvest.2017.19.
108. Bienkowski M, Preusser M. Prognostic role of tumour-infiltrating inflammatory cells in brain tumours: literature review. Curr Opin Neurol 2015; 28 (6): 647–658. doi: 10.1097/WCO.0000000000000251.
109. Gajewski TF, Louahed J, Brichard VG. Gene signature in melanoma associated with clinical activity: a potential clue to unlock cancer immunotherapy. Cancer J 2010; 16 (4): 399–403. doi: 10.1097/PPO.0b013e3181eacbd8.
110. Herbst RS, Soria JC, Kowanetz M et al. Predictive correlates of response to the anti-PD-L1 antibody MPDL3280A in cancer patients. Nature 2014; 515 (7528): 563–567. doi: 10.1038/nature14011.
111. Ji RR, Chasalow SD, Wang L et al. An immune-active tumor microenvironment favors clinical response to ipilimumab. Cancer Immunol Immunother 2012; 61 (7): 1019–1031. doi: 10.1007/s00262-011-1172-6.
112. Chen DS, Mellman I. Elements of cancer immunity and the cancer-immune set point. Nature 2017; 541 (7637): 321–330. doi: 10.1038/nature21349.
113. Inoue H, Tani K. Multimodal immunogenic cancer cell death as a consequence of anticancer cytotoxic treatments. Cell Death Differ 2014; 21 (1): 39–49. doi: 10.1038/cdd.2013.84.
114. Garg AD, Dudek-Peric AM, Romano E et al. Immunogenic cell death. Int J Dev Biol 2015; 59 (1–3): 131–140. doi: 10.1387/ijdb.150061pa.
115. Quail DF, Joyce JA. Microenvironmental regulation of tumor progression and metastasis. Nat Med 2013; 19 (11): 1423–1437. doi: 10.1038/nm.3394.
116. Fridman WH, Pages F, Sautes-Fridman C et al. The immune contexture in human tumours: impact on clinical outcome. Nat Rev Cancer 2012; 12 (4): 298–306. doi: 10.1038/nrc3245.
117. Sabeh F, Shimizu-Hirota R, Weiss SJ. Protease-dependent versus -independent cancer cell invasion programs: three-dimensional amoeboid movement revisited. J Cell Biol 2009; 185 (1): 11–19. doi: 10.1083/jcb.200807 195.
118. Angelosanto JM, Blackburn SD, Crawford A et al. Progressive loss of memory T cell potential and commitment to exhaustion during chronic viral infection. J Virol 2012; 86 (15): 8161–8170. doi: 10.1128/JVI.008 89-12.
Štítky
Paediatric clinical oncology Surgery Clinical oncologyČlánok vyšiel v časopise
Clinical Oncology
2017 Číslo Supplementum3
- Spasmolytic Effect of Metamizole
- Metamizole at a Glance and in Practice – Effective Non-Opioid Analgesic for All Ages
- Metamizole in perioperative treatment in children under 14 years – results of a questionnaire survey from practice
- Current Insights into the Antispasmodic and Analgesic Effects of Metamizole on the Gastrointestinal Tract
- Obstacle Called Vasospasm: Which Solution Is Most Effective in Microsurgery and How to Pharmacologically Assist It?
Najčítanejšie v tomto čísle
- Evaluation of Inflammatory Cells (Tumor Infiltrating Lymphocytes) in Solid Tumors
- Comparison of RECIST 1.1 and iRECIST for Response Evaluation in Solid Tumours
- Immunotherapy of Colorectal and Anal Carcinoma
- Imunoterapie v léčbě karcinomu plic