Tumor infiltrating lymphocytes (TIL) appears necessary to trigger anticancer activity of anti-PD-1/PD-L1. Radiomics consists in the analysis of quantitative data extracted from standard medical imaging to generate imaging biomarkers. We developed a radiomics-based predictor of TIL and investigated whether such signature could predict the outcome of patients treated by anti-PD1/PD-L1.
We first developed a predictive model of tumor infiltrating CD8 T cells with RNA-Seq and raw imaging data (CT –Scan) using random forest in 69 HNSCC patients from the TCGA (The Cancer Genome Atlas)/TCIA (The Cancer Imaging Archive) database. CD8 T cells were estimated by the Microenvironment Cell Populations-counter signature. To validate our tool, this signature was applied to a first independent cohort of 100 patients for which the pathologic TIL was assumed as either high (lymphoma, melanoma, lung, bladder, renal and MSI+ cancers; 30 patients) or low (adenoid cystic carcinoma, low-grade neuroendocrine tumors, uterine leiomyoma; 70 patients). Finally, we applied our signature on a second cohort of 139 patients prospectively enrolled in anti-PD-1/PD-L1 phase 1 trials to infer its relation with patient outcome (Overall Survival).
We developed a CD8 radiomics-based signature with six out of the 80 extracted features from CT-scans. As an internal validation, the correlation of this signature with the estimated TCGA CD8 was: spearman’s rho=0.81 (P
The radiomics-based signature of TIL was validated in two external cohorts. It appears a promising tool to estimate TIL and to infer the outcome of metastatic patients treated with anti-PD1/PD-L1.
Clinical trial identification
Legal entity responsible for the study
L. Verlingue: consulting Adaptherapy J-C. Soria: Consultancy fees from AstraZeneca, Astex, Clovis, GSK, Gammamabs, Lilly, MSD, Mission Therapeutics, Merus, Pfizer, Pharmamar Pierre Fabre, Roche-Genentech, Sanofi, Servier, Symphogen, Takeda. All other authors have declared no conflicts of interest.