scholarly journals Quantitative assessment of tumor-infiltrating lymphocytes in mismatch repair proficient colon cancer

2020 ◽  
Vol 9 (1) ◽  
pp. 1841948
Author(s):  
Rosa M. Jimenez-Rodriguez ◽  
Sujata Patil ◽  
Ajaratu Keshinro ◽  
Jinru Shia ◽  
Efsevia Vakiani ◽  
...  
2004 ◽  
Vol 20 (4-5) ◽  
pp. 215-224 ◽  
Author(s):  
Jeremy R. Jass

The aim of this paper is to indicate how the pathologist may suspect a diagnosis of hereditary non-polyposis colorectal cancer (HNPCC) on the basis of histological criteria and patient age alone. A single morphological feature, namely the presence of intra-epithelial lymphocytes (tumor infiltrating lymphocytes), identifies the majority of colorectal cancers (CRC) with the DNA microsatellite instability-high phenotype. A number of pathological criteria can help to distinguish HNPCC from sporadic MSI-H CRC, though age below 60 years is an important pointer towards HNPCC. Immunohistochemistry to demonstrate loss of expression of DNA mismatch repair genes serves as a highly reliable test of mismatch repair deficiency if antibodies to hMLH1, hMSH2, hMSH6 and hPMS2 are employed.


2021 ◽  
Vol 218 (9) ◽  
Author(s):  
Courtney Mowat ◽  
Shayla R. Mosley ◽  
Afshin Namdar ◽  
Daniel Schiller ◽  
Kristi Baker

Colorectal cancers (CRCs) deficient in DNA mismatch repair (dMMR) contain abundant CD8+ tumor-infiltrating lymphocytes (TILs) responding to the abundant neoantigens from their unstable genomes. Priming of such tumor-targeted TILs first requires recruitment of CD8+ T cells into the tumors, implying that this is an essential prerequisite of successful dMMR anti-tumor immunity. We have discovered that selective recruitment and activation of systemic CD8+ T cells into dMMR CRCs strictly depend on overexpression of CCL5 and CXCL10 due to endogenous activation of cGAS/STING and type I IFN signaling by damaged DNA. TIL infiltration into orthotopic dMMR CRCs is neoantigen-independent and followed by induction of a resident memory-like phenotype key to the anti-tumor response. CCL5 and CXCL10 could be up-regulated by common chemotherapies in all CRCs, indicating that facilitating CD8+ T cell recruitment underlies their efficacy. Induction of CCL5 and CXCL10 thus represents a tractable therapeutic strategy to induce TIL recruitment into CRCs, where local priming can be maximized even in neoantigen-poor CRCs.


Sign in / Sign up

Export Citation Format

Share Document