Thématique :
- Cancers autres (hors CCR et CHC)
Originalité :
Solidité :
Très solide
Doit faire évoluer notre pratique :
Dans certains cas
Nom du veilleur :
Professeur Sylvain MANFREDI
Coup de coeur :
Journal of the National Cancer Institute (JNCI)
  2018 Jan;110(1).  
  doi: 10.1093/jnci/djx136.  
  The Balance Between Cytotoxic T-cell Lymphocytes and Immune Checkpoint Expression in the Prognosis of Colon Tumors  
  Marisa L, Svrcek M, Collura A, Becht E, Cervera P, Wanherdrick K, Buhard O, Goloudina A, Jonchère V, Selves J, Milano G, Guenot D, Cohen R, Colas C, Laurent-Puig P, Olschwang S, Lefèvre JH, Parc Y, Boige V, Lepage C, André T, Fléjou JF, Dérangère V, Ghiringhelli F, de Reynies A, Duval A  



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.


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.


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).


ICK expression cancels the prognostic relevance of CTLs in highly immunogenic colon tumors and predicts a poor outcome in MSI CRC patients.


Question posée
L’expression des immune checkpoints est-elle pronostique ?
Question posée
Cette expression est pronostique pour les tumeurs « immunologiques » et est associée à un mauvais pronostic pour les tumeurs CMS1 et 4 (dont font partie les MSI).