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Does the Absence of Down-Regulation of MHC-I in Cancer Cells Necessarily Lead to their Annihilation by Immunologic Attack?

Pushpam Kumar Sinha

It has long been known now that MHC-I is down-regulated in several cancers and this has been linked with impaired immune attack against cancer cells. It is obvious then that low MHC-I expression is also linked with poor survival of cancer patients. But, however, through a careful analysis of the prognostic influence of MHC-I expression in colorectal cancer, head and neck squamous cell carcinoma, and biliary tract cancer, I conclude that the percentage of deaths of patients with high MHC-I expression in tumor (due to tumor alone) out of the total number of deaths (due to tumor alone) is not insignificant when compared to the percentage of deaths of cancer patients with low MHC-I expression in tumor. Hence the absence of down-regulation of MHC-I in cancer cells does not necessarily lead to their annihilation by immunologic attack. Stated differently, the down-regulation of MHC-I in cancer cells is not a necessary step in the genesis of cancer. New research needs to be directed at finding the immune evasion mechanism in cancer cells with high MHC-I expression. I finish the paper by speculating on few such mechanisms. Two of the important mechanisms speculated are clonal deletion of T cells (in the thymus) directed against antigens on Cancer Stem Cells, and down-regulation of MHC-II in metastatic cells which arise possibly by the fusion of hematopoietic stem cells and their lineages with tumor cells