Morgan E, Arnold M, Gina A, Lorenzoni V, Cabasag ML, Laversanne M, et al. Global burden of colorectal cancer in 2020 and 2040: incidence and mortality estimates from GLOBOCAN. Gut. 2023;72:228–344.

Article  Google Scholar 

Galon J, Costes A, Sanchez-Cabo F, Kirilovsky A, Mlecnik B, Lagorce-Pages C, et al. Type, density, and location of immune cells within human colorectal tumors predict clinical outcome. Science. 2006;313:1960–4.

Article  CAS  PubMed  Google Scholar 

Galon J, Mlecnik B, Bindea G, Angell HK, Berger A, Lagorce C, et al. Towards the introduction of the ‘Immunoscore’ in the classification of malignant tumours. J Pathol. 2014;232:199–209.

Article  CAS  PubMed  Google Scholar 

Deschoolmeester V, Baay M, Lardon F, Pauwels P, Peeters M. Immune cells in colorectal cancer: prognostic relevance and role of MSI. Cancer Microenviron. 2011;4:377–92.

Article  PubMed  PubMed Central  Google Scholar 

Palucka AK, Coussens LM. The basis of oncoimmunology. Cell. 2016;164:1233–47.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Le DT, Durham JN, Smith KN, Wang H, Bartlett BR, Aulakh LK, et al. Mismatch repair deficiency predicts response of solid tumors to PD-1 blockade. Science. 2017;357:409–13.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Poh A. A wow for Neoadjuvant ICI in dMMR colon cancer. Cancer Discov. 2022;12:2486–7.

Article  Google Scholar 

Cercek A, Lumish M, Sinopoli J, Weiss J, Shia J, Lamendola-Essel M, et al. PD-1 blockade in mismatch repair-deficient, locally advanced rectal cancer. N. Engl J Med. 2022;386:2363–76.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Baldus SE, Schaefer KL, Engers R, Hartleb D, Stoecklein NH, Gabbert HE. Prevalence and heterogeneity of KRAS, BRAF, and PIK3CA mutations in primary colorectal adenocarcinomas and their corresponding metastases. Clin Cancer Res. 2010;16:790–9.

Article  CAS  PubMed  Google Scholar 

Randrian V, Evrard C, Tougeron D. Microsatellite instability in colorectal cancers: carcinogenesis, neo-antigens, immuno-resistance and emerging therapies. Cancers. 2021;13:3063.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Mlecnik B, Bindea G, Angell HK, Maby P, Angelova M, Tougeron D, et al. Integrative analyses of colorectal cancer show immunoscore is a stronger predictor of patient survival than microsatellite instability. Immunity. 2016;44:698–711.

Article  CAS  PubMed  Google Scholar 

Domingo E, Freeman-Mills L, Rayner E, Glaire M, Briggs S, Vermeulen L, et al. Somatic POLE proofreading domain mutation, immune response, and prognosis in colorectal cancer: a retrospective, pooled biomarker study. Lancet Gastroenterol Hepatol. 2016;1:207–16.

Article  PubMed  Google Scholar 

Li X, Ling A, Kellgren TG, Lundholm M, Lofgren-Burstrom A, Zingmark C, et al. A detailed flow cytometric analysis of immune activity profiles in molecular subtypes of colorectal cancer. Cancers. 2020;12:3440.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Nebot-Bral L, Brandao D, Verlingue L, Rouleau E, Caron O, Despras E, et al. Hypermutated tumours in the era of immunotherapy: the paradigm of personalised medicine. Eur J Cancer. 2017;84:290–303.

Article  CAS  PubMed  Google Scholar 

Ahtiainen M, Wirta EV, Kuopio T, Seppala T, Rantala J, Mecklin JP, et al. Combined prognostic value of CD274 (PD-L1)/PDCDI (PD-1) expression and immune cell infiltration in colorectal cancer as per mismatch repair status. Mod Pathol. 2019;32:866–83.

Article  CAS  PubMed  Google Scholar 

Lee LH, Cavalcanti MS, Segal NH, Hechtman JF, Weiser MR, Smith JJ, et al. Patterns and prognostic relevance of PD-1 and PD-L1 expression in colorectal carcinoma. Mod Pathol. 2016;29:1433–42.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Rajagopalan H, Bardelli A, Lengauer C, Kinzler KW, Vogelstein B, Velculescu VE. Tumorigenesis: RAF/RAS oncogenes and mismatch-repair status. Nature. 2002;418:934.

Article  CAS  PubMed  Google Scholar 

Lochhead P, Kuchiba A, Imamura Y, Liao X, Yamauchi M, Nishihara R, et al. Microsatellite instability and BRAF mutation testing in colorectal cancer prognostication. J Natl Cancer Inst. 2013;105:1151–6.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Cen S, Liu K, Zheng Y, Shan J, Jing C, Gao J, et al. BRAF mutation as a potential therapeutic target for checkpoint inhibitors: a comprehensive analysis of immune microenvironment in BRAF mutated colon cancer. Front Cell Dev Biol. 2021;9:705060.

Article  PubMed  PubMed Central  Google Scholar 

Glimelius B, Melin B, Enblad G, Alafuzoff I, Beskow A, Ahlstrom H, et al. U-CAN: a prospective longitudinal collection of biomaterials and clinical information from adult cancer patients in Sweden. Acta Oncol. 2018;57:187–94.

Article  PubMed  Google Scholar 

Lowenmark T, Lofgren-Burstrom A, Zingmark C, Eklof V, Dahlberg M, Wai SN, et al. Parvimonas micra as a putative non-invasive faecal biomarker for colorectal cancer. Sci Rep. 2020;10:15250.

Article  PubMed  PubMed Central  Google Scholar 

Lowenmark T, Lofgren-Burstrom A, Zingmark C, Ljuslinder I, Dahlberg M, Edin S, et al. Tumour colonisation of parvimonas micra Is associated with decreased survival in colorectal cancer patients. Cancers. 2022;14:5937.

Article  PubMed  PubMed Central  Google Scholar 

Renman D, Gylling B, Vidman L, Boden S, Strigard K, Palmqvist R, et al. Density of CD3(+) and CD8(+) cells in the microenvironment of colorectal cancer according to prediagnostic physical activity. Cancer Epidemiol Biomark Prev. 2021;30:2317–26.

Article  CAS  Google Scholar 

Edin S, Kaprio T, Hagstrom J, Larsson P, Mustonen H, Bockelman C, et al. The prognostic importance of CD20(+) B lymphocytes in colorectal cancer and the relation to other immune cell subsets. Sci Rep. 2019;9:19997.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Sullivan BM, Juedes A, Szabo SJ, von Herrath M, Glimcher LH. Antigen-driven effector CD8 T cell function regulated by T-bet. Proc Natl Acad Sci USA. 2003;100:15818–23.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Mezheyeuski A, Micke P, Martin-Bernabe A, Backman M, Hrynchyk I, Hammarstrom K, et al. The immune landscape of colorectal cancer. Cancers. 2021;13:5545.

Inamura K. Colorectal cancers: an update on their molecular pathology. Cancers. 2018;10:26.

Article  PubMed  PubMed Central  Google Scholar 

Manda K, Glasow A, Paape D, Hildebrandt G. Effects of ionizing radiation on the immune system with special emphasis on the interaction of dendritic and T cells. Front Oncol. 2012;2:102.

Article  PubMed  PubMed Central  Google Scholar 

Carvalho HA, Villar RC. Radiotherapy and immune response: the systemic effects of a local treatment. Clinics. 2018;73:e557s.

Article  PubMed  Google Scholar 

Lim SH, Chua W, Cheng C, Descallar J, Ng W, Solomon M, et al. Effect of neoadjuvant chemoradiation on tumor-infiltrating/associated lymphocytes in locally advanced rectal cancers. Anticancer Res. 2014;34:6505–13.

CAS  PubMed  Google Scholar 

Matsutani S, Shibutani M, Maeda K, Nagahara H, Fukuoka T, Nakao S, et al. Significance of tumor-infiltrating lymphocytes before and after neoadjuvant therapy for rectal cancer. Cancer Sci. 2018;109:966–79.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Sakuyama N, Kojima M, Kawano S, Akimoto T, Saito N, Ito M, et al. Histological differences between preoperative chemoradiotherapy and chemotherapy for rectal cancer: a clinicopathological study. Pathol Int. 2016;66:273–80.

Article  PubMed  Google Scholar 

Angelova M, Charoentong P, Hackl H, Fischer ML, Snajder R, Krogsdam AM, et al. Characterization of the immunophenotypes and antigenomes of colorectal cancers reveals distinct tumor escape mechanisms and novel targets for immunotherapy. Genome Biol. 2015;16:64.

Article  PubMed  PubMed Central  Google Scholar 

Giannakis M, Mu XJ, Shukla SA, Qian ZR, Cohen O, Nishihara R, et al. Genomic correlates of immune-cell infiltrates in colorectal carcinoma. Cell Rep. 2016;17:1206.

Article  CAS  PubMed  PubMed Central  Google Scholar 

van den Bulk J, Verdegaal EME, Ruano D, Ijsselsteijn ME, Visser M, van der Breggen R, et al. Neoantigen-specific immunity in low mutation burden colorectal cancers of the consensus molecular subtype 4. Genome Med. 2019;11:87.

Article  PubMed  PubMed Central  Google Scholar 

Lal N, Beggs AD, Willcox BE, Middleton GW. An immunogenomic stratification of colorectal cancer: implications for development of targeted immunotherapy. Oncoimmunology. 2015;4:e976052.

Article  PubMed  PubMed Central  Google Scholar 

Ling A, Lundberg IV, Eklof V, Wikberg ML, Oberg A, Edin S, et al. The infiltration, and prognostic importance, of Th1 lymphocytes vary in molecular subgroups of colorectal cancer. J Pathol Clin Res. 2016;2:21–