2015
DOI: 10.18632/oncotarget.6179
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Mismatch repair gene defects in sporadic colorectal cancer enhance immune surveillance

Abstract: BackgroundThere is evidence that colorectal cancers (CRC) with DNA mismatch repair deficiency (MMR-D) are associated with a better prognosis than the generality of large bowel malignancies. Since an active immune surveillance process has been demonstrated to influence CRC outcome, we investigated whether MMR-D can enhance the immune response in CRC.Patients and MethodsA group of 113 consecutive patients operated for CRC (42 stage I or II and 71 with stage III or IV) was retrospectively analyzed. The expression… Show more

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Cited by 29 publications
(21 citation statements)
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“…Interestingly, our patient received a massive immunosuppressive load with anti-thymocyte globulins and a switch to a TAC plus MPS plus prednisone-based regimen after the episode of acute rejection, which occurred 6 months before the diagnosis of metastatic anal transitional zone adenocarcinoma. Moreover, this cancer showed an unexpected reduced T cell infiltration, contrary to what is usually observed in CRC with MMR defects or in UC-related CRC 19 , 20 . In fact, in our patient, CD4 and CD8 infiltration within the tumor was similar to that observed in post-transplant CRCs and lower than that observed in UC-related CRCs, suggesting a deep effect on cancer microenvironment of post-transplant immunosuppression regimen.…”
Section: Discussioncontrasting
confidence: 67%
“…Interestingly, our patient received a massive immunosuppressive load with anti-thymocyte globulins and a switch to a TAC plus MPS plus prednisone-based regimen after the episode of acute rejection, which occurred 6 months before the diagnosis of metastatic anal transitional zone adenocarcinoma. Moreover, this cancer showed an unexpected reduced T cell infiltration, contrary to what is usually observed in CRC with MMR defects or in UC-related CRC 19 , 20 . In fact, in our patient, CD4 and CD8 infiltration within the tumor was similar to that observed in post-transplant CRCs and lower than that observed in UC-related CRCs, suggesting a deep effect on cancer microenvironment of post-transplant immunosuppression regimen.…”
Section: Discussioncontrasting
confidence: 67%
“…The two patients whose tumors were MMR-D had unexpectedly sparse CD8 infiltration and a lack of PD-L1 expression. This is in contrast to reports on epithelial neoplasms where abundant CD8 infiltration was observed in MMR-D tumors such as colon, endometrial and gastric cancers [ 15 17 ].…”
Section: Discussioncontrasting
confidence: 99%
“…MMRd tumours have been demonstrated to be frequently PD‐L1‐positive . This could be explained by the characteristic accumulation of mutations in MMRd tumours, which results in the acquisition of unknown novel epitopes and the excessive activation of the immune system leading to the instigation of immunomodulatory mechanisms . Alterations in the MMR machinery are relatively frequent among AVCs, especially in the intestinal type .…”
Section: Discussionmentioning
confidence: 99%