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- Title
The Balance Between Cytotoxic T-cell Lymphocytes and Immune Checkpoint Expression in the Prognosis of Colon Tumors.
- Authors
Marisa, Laetitia; Svrcek, Magali; Collura, Ada; Becht, Etienne; Cervera, Pascale; Wanherdrick, Kristell; Buhard, Olivier; Goloudina, Anastasia; Jonchère, Vincent; Selves, Janick; Milano, Gerard; Guenot, Dominique; Cohen, Romain; Colas, Chrystelle; Laurent-Puig, Pierre; Olschwang, Sylviane; Lefévre, Jérémie H.; Parc, Yann; Ghiringhelli, François; de Reynies, Aurélien
- Abstract
<bold>Background: </bold>Immune checkpoint (ICK) expression might represent a surrogate measure of tumor-infiltrating T cell (CTL) exhaustion and therefore be a more accurate prognostic biomarker for colorectal cancer (CRC) patients than CTL enumeration as measured by the Immunoscore.<bold>Methods: </bold>The expression of ICKs, Th1, CTLs, cytotoxicity-related genes, and metagenes, including Immunoscore-like metagenes, were evaluated in three independent cohorts of CRC samples (260 microsatellite instable [MSI], 971 non-MSI). Their associations with patient survival were analyzed by Cox models, taking into account the microsatellite instability (MSI) status and affiliation with various Consensus Molecular Subgroups (CMS). PD-L1 and CD8 expression were examined on a subset of tumors with immunohistochemistry. All statistical tests were two-sided.<bold>Results: </bold>The expression of Immunoscore-like metagenes was statistically significantly associated with improved outcome in non-MSI tumors displaying low levels of both CTLs and immune checkpoints (ICKs; CMS2 and CMS3; hazard ratio [HR] = 0.63, 95% confidence interval [CI] = 0.43 to 0.92, P = .02; and HR = 0.55, 95% CI = 0.34 to 0.90, P = .02, respectively), but clearly had no prognostic relevance in CRCs displaying higher levels of CTLs and ICKs (CMS1 and CMS4; HR = 0.46, 95% CI = 0.10 to 2.10, P = .32; and HR = 1.13, 95% CI = 0.79 to 1.63, P = .50, respectively), including MSI tumors. ICK metagene expression was statistically significantly associated with worse prognosis independent of tumor staging in MSI tumors (HR = 3.46, 95% CI = 1.41 to 8.49, P = .007). ICK expression had a negative impact on the proliferation of infiltrating CD8 T cells in MSI neoplasms (median = 0.56 in ICK low vs median = 0.34 in ICK high, P = .004).<bold>Conclusions: </bold>ICK expression cancels the prognostic relevance of CTLs in highly immunogenic colon tumors and predicts a poor outcome in MSI CRC patients.
- Subjects
ANTIGEN analysis; ANTIGENS; COLON (Anatomy); COLON tumors; COMPARATIVE studies; DEGENERATION (Pathology); GENE expression; LYMPHOCYTES; RESEARCH methodology; MEDICAL cooperation; PROGNOSIS; RECTUM tumors; RESEARCH; SURVIVAL; T cells; TUMOR classification; EVALUATION research; RETROSPECTIVE studies
- Publication
JNCI: Journal of the National Cancer Institute, 2018, Vol 110, Issue 1, p1
- ISSN
0027-8874
- Publication type
journal article
- DOI
10.1093/jnci/djx136