Neoadjuvant radiochemotherapy decreases the total amount of tumor infiltrating lymphocytes, but increases the number of CD8+/Granzyme B+ (GrzB) cytotoxic T-cells in rectal cancer

References

• Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A. Global cancer statistics, 2012. CA Cancer J Clin. 2015;65:87–108. eng. doi:10.3322/caac.21262. PMID:25651787
   PubMed Web of Science ®Google Scholar
• Krebs in Deutschland 2011/2012. 10. Ausgabe. Robert Koch-Institut und die Gesellschaft der epidemiologischen Krebsregister in Deutschland e.V. (Hrsg). Berlin, 2015. ISBN 978-3-89606-228-4. doi:10.17886/rkipubl-2015-004
   Google Scholar
• American Cancer Society. Cancer Facts & Figures 2017. Atlanta, Ga 2017 [Available from: https://www.cancer.org/content/dam/cancer-org/research/cancer-facts-and-statistics/annual-cancer-facts-and-figures/2017/cancer-facts-and-figures-2017.pdf]
   Google Scholar
• Hafner MF, Debus J. Radiotherapy for Colorectal Cancer: Current Standards and Future Perspectives. Visc Med. 2016;32:172–177. eng. doi:10.1159/000446486. doi:10.1159/000446486. PMID:27493944
   PubMed Web of Science ®Google Scholar
• Li Y, Wang J, Ma X, Tan L, Yan Y, Xue C, Hui B, Liu R, Ma H, Ren J. A Review of Neoadjuvant Chemoradiotherapy for Locally Advanced Rectal Cancer. Int J Biol Sci. 2016;12:1022–1031. eng. doi:10.7150/ijbs.15438. doi:10.7150/ijbs.15438. PMID:27489505
   PubMed Web of Science ®Google Scholar
• Dworak O, Keilholz L, Hoffmann A. Pathological features of rectal cancer after preoperative radiochemotherapy. Int J Colorectal Dis. 1997;12:19–23. eng. doi:10.1007/s003840050072. PMID:9112145
   PubMed Web of Science ®Google Scholar
• Thies S, Langer R. Tumor regression grading of gastrointestinal carcinomas after neoadjuvant treatment. Front Oncol. 2013;3:262. eng. doi:10.3389/fonc.2013.00262. PMID:24109590
   PubMedGoogle Scholar
• Rodel C, Martus P, Papadoupolos T, Fuzesi L, Klimpfinger M, Fietkau R, Liersch T, Hohenberger W, Raab R, Sauer R, Wittekind C. Prognostic significance of tumor regression after preoperative chemoradiotherapy for rectal cancer. J Clin Oncol. 2005;23:8688–8696. eng. doi:10.1200/JCO.2005.02.1329. PMID:16246976
   PubMed Web of Science ®Google Scholar
• Jakob C, Liersch T, Meyer W, Baretton GB, Schwabe W, Hausler P, Kulle B, Becker H, Aust DE. Prognostic value of histologic tumor regression, thymidylate synthase, thymidine phosphorylase, and dihydropyrimidine dehydrogenase in rectal cancer UICC Stage II/III after neoadjuvant chemoradiotherapy. Am J Surg Pathol. 2006;30:1169–1174. eng. doi:10.1097/01.pas.0000213302.13435.6e. PMID:16931962
   PubMed Web of Science ®Google Scholar
• Cunningham D, Atkin W, Lenz H, Lynch HT, Minsky B, Nordlinger B, Starling N. 2010. Colorectal cancer. Lancet. 375:1030–1047. eng. doi:10.1016/S0140-6736(10)60353-4. PMID:20304247
   PubMed Web of Science ®Google Scholar
• Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011;144:646–674. eng. doi:10.1016/j.cell.2011.02.013. PMID:21376230
   PubMed Web of Science ®Google Scholar
• Gooden MJM, Bock GH de, Leffers N, Daemen T, Nijman HW. 2011. The prognostic influence of tumour-infiltrating lymphocytes in cancer: a systematic review with meta-analysis. Br J Cancer. 105:93–103. eng. doi:10.1038/bjc.2011.189.
   PubMed Web of Science ®Google Scholar
• Denkert C, Loibl S, Noske A, Roller M, Muller BM, Komor M, Budczies J, Darb-Esfahani S, Kronenwett R, Hanusch C, et al. Tumor-associated lymphocytes as an independent predictor of response to neoadjuvant chemotherapy in breast cancer. J Clin Oncol. 2010;28:105–113. eng. doi:10.1200/JCO.2009.23.7370. PMID:19917869
   PubMed Web of Science ®Google Scholar
• Balermpas P, Rodel F, Rodel C, Krause M, Linge A, Lohaus F, Baumann M, Tinhofer I, Budach V, Gkika E, et al. CD8+ tumour-infiltrating lymphocytes in relation to HPV status and clinical outcome in patients with head and neck cancer after postoperative chemoradiotherapy: A multicentre study of the German cancer consortium radiation oncology group (DKTK-ROG). Int J Cancer. 2016;138:171–181. eng. doi:10.1002/ijc.29683. PMID:26178914
   PubMed Web of Science ®Google Scholar
• Leffers N, Gooden MJM, Jong RA de, Hoogeboom B-N, Hoor KA ten, Hollema H, Boezen HM, van der Zee AGJ, Daemen T, Nijman HW. Prognostic significance of tumor-infiltrating T-lymphocytes in primary and metastatic lesions of advanced stage ovarian cancer. Cancer Immunol Immunother. 2009;58:449–459. eng. doi:10.1007/s00262-008-0583-5. PMID:18791714
   PubMed Web of Science ®Google Scholar
• Mei Z, Liu Y, Liu C, Cui A, Liang Z, Wang G, Peng H, Cui L, Li C. Tumour-infiltrating inflammation and prognosis in colorectal cancer: systematic review and meta-analysis. Br J Cancer. 2014;110:1595–1605. eng. doi:10.1038/bjc.2014.46.
   PubMed Web of Science ®Google Scholar
• Galon J, Costes A, Sanchez-Cabo F, Kirilovsky A, Mlecnik B, Lagorce-Pages C, Tosolini M, Camus M, Berger A, Wind P, et al. 2006. Type, density, and location of immune cells within human colorectal tumors predict clinical outcome. Science. 313:1960–1964. eng. doi:10.1126/science.1129139. PMID:17008531
   PubMed Web of Science ®Google Scholar
• Wittekind C, editor. TNM-Klassifikation maligner Tumoren [Internet]. Achte Auflage. Weinheim: Wiley-VCH Verlag GmbH & Co. KGaA; 2017. 313 p. ISBN: 9783527807598. ger.
   Google Scholar
• Daster S, Eppenberger-Castori S, Hirt C, Soysal SD, Delko T, Nebiker CA, Weixler B, Amicarella F, Iezzi G, Governa V, et al. 2015. Absence of myeloperoxidase and CD8 positive cells in colorectal cancer infiltrates identifies patients with severe prognosis. Oncoimmunology. 4:e1050574. eng. doi:10.1080/2162402X.2015.1050574. PMID:26587320
   PubMed Web of Science ®Google Scholar
• Bots M, Medema JP. Granzymes at a glance. J Cell Sci. 2006;119:5011–5014. eng. doi:10.1242/jcs.03239. PMID:17158907
   PubMed Web of Science ®Google Scholar
• Kuerer HM, Newman LA, Smith TL, Ames FC, Hunt KK, Dhingra K, Theriault RL, Singh G, Binkley SM, Sneige N, et al. Clinical course of breast cancer patients with complete pathologic primary tumor and axillary lymph node response to doxorubicin-based neoadjuvant chemotherapy. J Clin Oncol. 1999;17:460–469. eng. doi:10.1200/JCO.1999.17.2.460. PMID:10080586
   PubMed Web of Science ®Google Scholar
• Teng F, Meng X, Kong L, Mu D, Zhu H, Liu S, Zhang J, Yu J. Tumor-infiltrating lymphocytes, forkhead box P3, programmed death ligand-1, and cytotoxic T lymphocyte-associated antigen-4 expressions before and after neoadjuvant chemoradiation in rectal cancer. Transl Res. 2015;166:721–732. e1. eng. doi:10.1016/j.trsl.2015.06.019. PMID:26209749
   PubMed Web of Science ®Google Scholar
• Kim JH, Kang GH. Molecular and prognostic heterogeneity of microsatellite-unstable colorectal cancer. World J Gastroenterol. 2014;20:4230–4243. eng. doi:10.3748/wjg.v20.i15.4230. PMID:24764661
   PubMed Web of Science ®Google Scholar
• Shia J, Ellis NA, Paty PB, Nash GM, Qin J, Offit K, Zhang X, Markowitz AJ, Nafa K, Guillem JG, et al. Value of histopathology in predicting microsatellite instability in hereditary nonpolyposis colorectal cancer and sporadic colorectal cancer. Am J Surg Pathol. 2003;27:1407–1417. eng. doi:10.1097/00000478-200311000-00002. PMID:14576473
   PubMed Web of Science ®Google Scholar
• McShane LM, Altman DG, Sauerbrei W, Taube SE, Gion M, Clark GM. REporting recommendations for tumour MARKer prognostic studies (REMARK). Br J Cancer. 2005;93:387–391. doi:10.1038/sj.bjc.6602678. PMID:16106245
   PubMed Web of Science ®Google Scholar
• Roxburgh CSD, McMillan DC. The role of the in situ local inflammatory response in predicting recurrence and survival in patients with primary operable colorectal cancer. Cancer Treat Rev. 2012;38:451–466. eng. doi:10.1016/j.ctrv.2011.09.001. PMID:21945823
   PubMed Web of Science ®Google Scholar
• Order SE. The effects of therapeutic irradiation on lymphocytes and immunity. Cancer. 1977;39:737–743. eng. doi:10.1002/1097-0142(197702)39:2+%3c737::AID-CNCR2820390708%3e3.0.CO;2-M. PMID:300040
   PubMed Web of Science ®Google Scholar
• Richards CH, Roxburgh CSD, Powell AG, Foulis AK, Horgan PG, McMillan DC. The clinical utility of the local inflammatory response in colorectal cancer. Eur J Cancer. 2014;50:309–319. eng. doi:10.1016/j.ejca.2013.09.008. PMID:24103145
   PubMed Web of Science ®Google Scholar
• Teng F, Meng X, Kong L, Mu D, Zhu H, Liu S, Zhang J, Yu J. Tumor-infiltrating lymphocytes, forkhead box P3, programmed death ligand-1, and cytotoxic T lymphocyte-associated antigen-4 expressions before and after neoadjuvant chemoradiation in rectal cancer. Transl Res. 2015;166:721. eng. doi:10.1016/j.trsl.2015.06.019. PMID:26209749
   PubMed Web of Science ®Google Scholar
• Sato E, Olson SH, Ahn J, Bundy B, Nishikawa H, Qian F, Jungbluth AA, Frosina D, Gnjatic S, Ambrosone C, et al. Intraepithelial CD8+ tumor-infiltrating lymphocytes and a high CD8+/regulatory T cell ratio are associated with favorable prognosis in ovarian cancer. Proc Natl Acad Sci U S A. 2005;102:18538–18543. eng. doi:10.1073/pnas.0509182102. PMID:16344461
   PubMed Web of Science ®Google Scholar
• McCoy MJ, Hemmings C, Hillery S, Penter C, Bulsara MK, Zeps N, Platell CF. Neoadjuvant chemoradiotherapy for rectal cancer: how important is tumour regression? ANZ J Surg. 2015; eng. doi:10.1111/ans.13394. PMID:26631340
   PubMed Web of Science ®Google Scholar
• Sauer R, Becker H, Hohenberger W, Rodel C, Wittekind C, Fietkau R, Martus P, Tschmelitsch J, Hager E, Hess CF, et al. Preoperative versus postoperative chemoradiotherapy for rectal cancer. N engl J Med. 2004;351:1731–1740. eng. doi:10.1056/NEJMoa040694. PMID:15496622
   PubMed Web of Science ®Google Scholar
• Matsumura S, Wang B, Kawashima N, Braunstein S, Badura M, Cameron TO, Babb JS, Schneider RJ, Formenti SC, Dustin ML, Demaria S. Radiation-induced CXCL16 release by breast cancer cells attracts effector T-cells. J Immunol. 2008;181:3099–3107. eng. doi:10.4049/jimmunol.181.5.3099. PMID:18713980
   PubMed Web of Science ®Google Scholar
• Rousalova I, Krepela E, Granzyme B-induced apoptosis in cancer cells and its regulation (review). Int J Oncol. 2010;37(6):1361–78. eng. PMID:21042704
   PubMed Web of Science ®Google Scholar