Impaired CD95 Expression Predisposes for Recurrence in Curatively Resected Colon Carcinoma: Clinical Evidence for Immunoselection and CD95L Mediated Control of Minimal Residual Disease
Overview
Affiliations
Background: Loss of CD95 expression in tumour cells occurs frequently in colon carcinoma and may be associated with disease progression. On the other hand, neo-expression of CD95L in tumour cells may contribute to immune evasion.
Aims: We aimed at further exploring the functional role and prognostic significance of the CD95/CD95L death inducing system in colon carcinomas.
Patients And Methods: CD95 and CD95L expression was examined by immunohistochemistry in 128 R0 resected UICC (International Union against Cancer) stage II/III colon carcinomas and correlated with disease free survival.
Results: CD95 expression in tumour cells was observed in only 30 carcinomas (23.4%) whereas the others had at least a minor subpopulation of CD95 negative cells. Loss of CD95 in tumour cells was related to adverse prognosis in uni- and multivariate analysis (p = 0.046 and p = 0.036, respectively). Tumour infiltrating lymphocytes (TIL) were the major source of CD95L in colon carcinomas. CD95L+TIL were present in 83% of cases whereas CD95L was found in tumour cells in only 12% of cases. Moreover, a high rate of CD95L+TIL correlated with prolonged disease free survival in patients with UICC stage II (p = 0.05) but not in those with stage III.
Conclusions: Loss of CD95 in tumour cells may be an independent prognostic factor in colon carcinomas. The CD95L counterattack is not a relevant feature in colon carcinoma but CD95L+TIL may contribute to tumour control in the early stages of the disease, exerting a concurrent selection pressure in the direction of CD95 abrogation/resistance.
Role of metalloproteases in the CD95 signaling pathways.
Devel L, Guedeney N, Bregant S, Chowdhury A, Jean M, Legembre P Front Immunol. 2022; 13:1074099.
PMID: 36544756 PMC: 9760969. DOI: 10.3389/fimmu.2022.1074099.
Lipid Nanoparticle Delivery of Fas Plasmid Restores Fas Expression to Suppress Melanoma Growth .
Al Subeh Z, Poschel D, Redd P, Klement J, Merting A, Yang D ACS Nano. 2022; 16(8):12695-12710.
PMID: 35939651 PMC: 9721370. DOI: 10.1021/acsnano.2c04420.
MicroRNA-Assisted Hormone Cell Signaling in Colorectal Cancer Resistance.
Massaro C, Safadeh E, Sgueglia G, Stunnenberg H, Altucci L, DellAversana C Cells. 2021; 10(1).
PMID: 33396628 PMC: 7823834. DOI: 10.3390/cells10010039.
Saha N, Muntean A Biochim Biophys Acta Rev Cancer. 2020; 1875(1):188498.
PMID: 33373647 PMC: 7856268. DOI: 10.1016/j.bbcan.2020.188498.
SUV39H1 regulates human colon carcinoma apoptosis and cell cycle to promote tumor growth.
Lu C, Klement J, Yang D, Albers T, Lebedyeva I, Waller J Cancer Lett. 2020; 476:87-96.
PMID: 32061753 PMC: 7138631. DOI: 10.1016/j.canlet.2020.02.004.