Tumour-infiltrating lymphocytes in colorectal cancer with microsatellite instability are activated and cytotoxic

Abstract

The results support the hypothesis that MSI-H colorectal cancers may be more immunogenic than MSS tumours.

The current value of determining the mismatch repair status of colorectal cancer: A rationale for routine testing

“…The assumed better prognoses of MSI CRC may reflect the marked T cell infiltration related to the specific antigen-driven immune responses caused by dMMR (Phillips et al, 2004). The numerous frameshift mutations that result cause the production of truncated, functionally inactive proteins.…”

Immune Cells in Colorectal Cancer: Prognostic Relevance and Role of MSI

“…In contrast, pronounced lymphocytic infiltration is marked in high-graded microsatellite instable (MSI-H) CRC and might explain the better clinical outcome in these patients [64]. It has been postulated that MSI-H CRC are more immunogenic than microsatellite stable (MSS) tumors because of the generation of a large number of abnormal peptides by frameshift mutations [49,[65][66][67][68][69][70]. However, in the analysis of Chiba et al [52] there was no significant increase in the number of CD8 + IEL in cases with MSI.…”

“…However, in the analysis of Chiba et al [52] there was no significant increase in the number of CD8 + IEL in cases with MSI. Therefore, it appears that although MSI could be associated with a high infiltration of T cells in tumor tissue, additional mechanisms like cross-priming of antigen-presenting cells by released intracellular antigens or the use of HLA class II machinery and T helper cell activity may provide an alternative pathway for immune stimulation in vivo [41,65,67].…”

High density of FOXP3-positive T cells infiltrating colorectal cancers with microsatellite instability

“…Although the majority of CRCs is hallmarked by large chromosomal alterations (Lengauer et al, 1997), about 10-15% of CRCs are characterised by the high-level microsatellite instability (MSI-H) phenotype that results from defects in the DNA mismatch repair system. The anti-tumoural immune response against CRCs is apparently closely linked to the molecular pathogenesis of these tumours, and MSI-H CRCs typically present with features of a pronounced local immune response, for example a high density of tumour-infiltrating lymphocytes with a high proportion of activated and cytotoxic CD8-positive lymphocytes (Dolcetti et al, 1999;Smyrk et al, 2001;Phillips et al, 2004;Jenkins et al, 2007). In line with the pronounced immunogenicity of MSI-H CRCs, these cancers rarely develop metastases in distant organs and have a comparably good prognosis (Buckowitz et al, 2005;Popat et al, 2005) in spite of a large tumour mass at the primary localisation (Wright et al, 2000).…”