TY - JOUR
T1 - Dissecting tumor lymphocyte infiltration to predict benefit from immune-checkpoint inhibitors in metastatic colorectal cancer: Lessons from the AtezoT RIBE study
AU - Moretto, R.
AU - Rossini, D.
AU - Catteau, A.
AU - Antoniotti, C.
AU - Giordano, M.
AU - Boccaccino, A.
AU - Ugolini, C.
AU - Proietti, A.
AU - Conca, V.
AU - Kassambara, A.
AU - Pietrantonio, Filomena
AU - Salvatore, Lisa
AU - Lonardi, S.
AU - Tamberi, S.
AU - Tamburini, E.
AU - Poma, A. M.
AU - Fieschi, J.
AU - Fontanini, G.
AU - Masi, G.
AU - Galon, J.
AU - Cremolini, C.
PY - 2023
Y1 - 2023
N2 - Background Tumor immune cells influence the efficacy of immune-checkpoint inhibitors (ICIs) and many efforts aim at identifying features of tumor immune microenvironment able to predict benefit from ICIs in proficient mismatch repair (pMMR)/microsatellite stable (MSS) metastatic colorectal cancer (mCRC). Methods We characterized tumor immune cell infiltrate, by assessing tumor-infiltrating lymphocytes (TILs), Immunoscore, Immunoscore-IC, and programmed death ligand-1 (PD-L1) expression in tumor samples of patients with mCRC enrolled in the AtezoTRIBE study, a phase II randomized trial comparing FOLFOXIRI/bevacizumab/atezolizumab to FOLFOXIRI/bevacizumab, with the aim of evaluating the prognostic and predictive value of these features. Results Out of 218 patients enrolled, 181 (83%), 77 (35%), 157 (72%) and 162 (74%) specimens were successfully tested for TILs, Immunoscore, Immunoscore-IC and PD-L1 expression, respectively, and 69 (38%), 45 (58%), 50 (32%) and 21 (13%) tumors were classified as TILs-high, Immunoscore-high, Immunoscore-IC-high and PD-L1-high, respectively. A poor agreement was observed between TILs and Immunoscore or Immunoscore-IC (K of Cohen <0.20). In the pMMR population, longer progression-free survival (PFS) was reported for Immunoscore-high and Immunoscore-IC-high groups compared with Immunoscore-low (16.4 vs 12.2 months; HR: 0.55, 95% CI: 0.30 to 0.99; p=0.049) and Immunoscore-IC-low (14.8 vs 11.5 months; HR: 0.55, 95% CI: 0.35 to 0.85; p=0.007), respectively, with a significant interaction effect between treatment arms and Immunoscore-IC (p for interaction: 0.006) and a trend for Immunoscore (p for interaction: 0.13). No PFS difference was shown according to TILs and PD-L1 expression. Consistent results were reported in the overall population. Conclusions The digital evaluation of tumor immune cell infiltrate by means of Immunoscore-IC or Immunoscore identifies the subset of patients with pMMR mCRC achieving more benefit from the addition of the anti-PD-L1 to the upfront treatment. Immunoscore-IC stands as the most promising predictor of benefit from ICIs.
AB - Background Tumor immune cells influence the efficacy of immune-checkpoint inhibitors (ICIs) and many efforts aim at identifying features of tumor immune microenvironment able to predict benefit from ICIs in proficient mismatch repair (pMMR)/microsatellite stable (MSS) metastatic colorectal cancer (mCRC). Methods We characterized tumor immune cell infiltrate, by assessing tumor-infiltrating lymphocytes (TILs), Immunoscore, Immunoscore-IC, and programmed death ligand-1 (PD-L1) expression in tumor samples of patients with mCRC enrolled in the AtezoTRIBE study, a phase II randomized trial comparing FOLFOXIRI/bevacizumab/atezolizumab to FOLFOXIRI/bevacizumab, with the aim of evaluating the prognostic and predictive value of these features. Results Out of 218 patients enrolled, 181 (83%), 77 (35%), 157 (72%) and 162 (74%) specimens were successfully tested for TILs, Immunoscore, Immunoscore-IC and PD-L1 expression, respectively, and 69 (38%), 45 (58%), 50 (32%) and 21 (13%) tumors were classified as TILs-high, Immunoscore-high, Immunoscore-IC-high and PD-L1-high, respectively. A poor agreement was observed between TILs and Immunoscore or Immunoscore-IC (K of Cohen <0.20). In the pMMR population, longer progression-free survival (PFS) was reported for Immunoscore-high and Immunoscore-IC-high groups compared with Immunoscore-low (16.4 vs 12.2 months; HR: 0.55, 95% CI: 0.30 to 0.99; p=0.049) and Immunoscore-IC-low (14.8 vs 11.5 months; HR: 0.55, 95% CI: 0.35 to 0.85; p=0.007), respectively, with a significant interaction effect between treatment arms and Immunoscore-IC (p for interaction: 0.006) and a trend for Immunoscore (p for interaction: 0.13). No PFS difference was shown according to TILs and PD-L1 expression. Consistent results were reported in the overall population. Conclusions The digital evaluation of tumor immune cell infiltrate by means of Immunoscore-IC or Immunoscore identifies the subset of patients with pMMR mCRC achieving more benefit from the addition of the anti-PD-L1 to the upfront treatment. Immunoscore-IC stands as the most promising predictor of benefit from ICIs.
KW - Immune Checkpoint Inhibitors
KW - Tumor Microenvironment
KW - T-Lymphocytes
KW - Immunotherapy
KW - Immune Checkpoint Inhibitors
KW - Tumor Microenvironment
KW - T-Lymphocytes
KW - Immunotherapy
UR - http://hdl.handle.net/10807/304449
U2 - 10.1136/jitc-2022-006633
DO - 10.1136/jitc-2022-006633
M3 - Article
SN - 2051-1426
VL - 11
SP - N/A-N/A
JO - Journal for ImmunoTherapy of Cancer
JF - Journal for ImmunoTherapy of Cancer
ER -