Changes in the CD8+ Density of Tumor Infiltrating Lymphocytes after Neoadjuvant Radiochemotherapy in Patients with Rectal Adenocarcinom
Authors:
D. Buka 1; J. Dvořák 2
; V. Sitorová 3; J. Hátlová 3; I. Richter 4; I. Sirák 1
Authors place of work:
Klinika onkologie a radioterapie LF UK a FN Hradec Králové
1; Onkologická klinika 1. LF UK a Thomayerova nemocnice, Praha
2; Fingerlandův ústav patologie, LF UK a FN Hradec Králové
3; Oddělení klinické onkologie, Krajská nemocnice Liberec, a. s.
4
Published in the journal:
Klin Onkol 2016; 29(3): 204-209
Category:
Original Articles
doi:
https://doi.org/10.14735/amko2016204
Summary
Background:
The goal of this study is to examine the effect of neoadjuvant radiochemotherapy on the density of CD8+ tumor infiltrating lymphocytes (TILs) in endoscopical biopsies and resection specimens from patients with rectal adenocarcinoma before and after therapy.
Patients and Methods:
In total, 53 patients with locally advanced rectal cancer were studied.
Results:
The median density of CD8+ TILs in pretreatment biopsies was 12 (1– 232) and that in surgical specimens after radiochemotherapy was 18 (1– 319). During radiochemotherapy, the density of CD8+ TILs increased in 30 patients (57%), decreased in 18 (34%), and did not change in one. It was not possible to assess the dynamics of CD8+ TILs density in four patients. The increased density of CD8+ TILs after radiochemotherapy was associated with a median survival rate 2.5 times longer than that associated with no increase in density.
Conclusion:
In the present study, the density of CD8+ TILs in endoscopical biopsies before radiochemotherapy, the density in resection specimens after radiochemotherapy, or in changes in the density after radiochemotherapy showed no predictive or prognostic significance. However, studying a larger number of patients may show that CD8+ TILs density is of predictive or prognostic significance.
Key words:
rectal adenocarcinoma – preoperative treatment – radiochemotherapy – immunoscore – CD8+ tumor infiltrating lymphocytes
This study was supported by project PRVOUK P37/01 and PRVOUK P37/11.
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:
5. 11. 2015
Accepted:
9. 1. 2016
Zdroje
1. Dvořák J, Richter I, Buka D et al. Chemoradioterapeutická léčba lokálně pokročilých karcinomů rekta. Farmakoterapie Kolorektální karcinom 2013: 42– 46.
2. Richter I, Dvořák J, Bartoš J. Neoadjuvantní léčba karcinomu rekta. Onkologie 2013; 7(6): 287– 290.
3. Pilones KA, Vanpouille-Box C, Demaria S. Combination of radiotherapy and immune checkpoint inhibitors. Semin Radiat Oncol 2015; 25(1): 28– 33. doi: 10.1016/ j.semradonc.2014.07.004.
4. Wattenberg MM, Fahim A, Ahmed MM et al. Unlocking the combination: potentiation of radiation-induced antitumor responses with immunotherapy. Radiat Res 2014; 182(2): 126– 138. doi: 10.1667/ RR13374.1.
5. Formenti SC, Demaria S. Combining radiotherapy and cancer immunotherapy: a paradigm shift. J Natl Cancer Inst 2013; 105(4): 256– 265. doi: 10.1093/ jnci/ djs629.
6. Demaria S, Pilones KA, Vanpouille-Box C et al. The optimal partnership of radiation and immunotherapy: from preclinical studies to clinical translation. Radiat Res 2014; 182(2): 170– 181. doi: 10.1667/ RR13500.1.
7. Kopecký J, Slováček L, Priester P et al. Změny imunologické reaktivity u onkologických pacientů. Klin Onkol 2012; 25(2): 97– 102. doi: 10.14735/ amko201297.
8. Lee Y, Auh SL, Wang Y et al. Therapeutic effects of ablative radiation on local tumor require CD8+ T cells: changing strategies for cancer treatment. Blood 2009; 114(3): 589– 595. doi: 10.1182/ blood-2009-02-206870.
9. Crittenden M, Kohrt H, Levy R et al. Current clinical trials testing combinations of immunotherapy and radiation. Semin Radiat Oncol 2015; 25(1): 54– 64. doi: 10.1016/ j.semradonc.2014.07.003.
10. Reynders K, Illidge T, Siva S et al. The abscopal effect of local radiotherapy: using immunotherapy to make a rare event clinically relevant. Cancer Treat Rev 2015; 41(6): 503– 510. doi: 10.1016/ j.ctrv.2015.03.011.
11. Postow MA, Callahan MK, Barker CA et al. Immunologic correlates of the abscopal effect in a patient with melanoma. N Engl J Med 2012; 366(10): 925– 931. doi: 10.1056/ NEJMoa1112824.
12. 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.
13. Fridman WH, Dieu-Nosjean MC, Pagès F et al. The immune microenvironment of human tumors: general significance and clinical impact. Cancer Microenviron 2013; 6(2): 117– 122. doi: 10.1007/ s12307-012-0124-9.
14. Galon J, Pagès F, Marincola FM et al. Cancer classification using the Immunoscore: a worldwide task force. J Transl Med 2012; 10: 205. doi: 10.1186/ 1479-5876-10-205.
15. Soukup K, Wang X. Radiation meets immunotherapy – a perfect match in the era of combination therapy? Int J Radiat Biol 2015; 91(4): 299– 305. doi: 10.3109/ 09553002.2014.995383.
16. National Cancer Institute [homepage on the Internet]. Common Toxicity Criteria for Adverse Events v 4.0 (CTCAE). Available from: http:/ / ctep.cancer.gov.
17. Teng F, Mu D, Meng X et al. Tumor infiltrating lymphocytes (TILs) before and after neoadjuvant chemoradiotherapy and its clinical utility for rectal cancer. Am J Cancer Res 2015; 5(6): 2064– 2074.
18. Ropponen KM, Eskelinen MJ, Lipponen PK et al. Prognostic value of tumour-infiltrating lymphocytes (TILs) in colorectal cancer. J Pathol 1997; 182(3): 318– 324.
19. Chiba T, Ohtani H, Mizoi T et al. Intraepithelial CD8+ T-cell-count becomes a prognostic factor after a longer follow-up period in human colorectal carcinoma: possible association with suppression of micrometastasis. Br J Cancer 2004; 91(9): 1711– 1717.
20. 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.
21. Pagès 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.
22. 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.
23. Alexandrov LB, Nik-Zainal S, Wedge DC et al. Signatures of mutational processes in human cancer. Nature 2013; 500(7463): 415– 421. doi: 10.1038/ nature12477.
24. Maby P, Tougeron D, Hamieh M et al. Correlation between density of CD8+ T-cell infiltrate in microsatellite unstable colorectal cancers and frameshift mutations: a rationale for personalized immunotherapy. Cancer Res 2015; 75(17): 3446– 3455. doi: 10.1158/ 0008-5472.CAN-14-3051.
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