Background Evidence supports the association between tumor-infiltrating lymphocytes with disease prognosis and response to immunotherapy. Here, we evaluated the prognostic value of an immunoscore reflecting CD3+ and CD8+ T cell density in patients with advanced malignancies treated with immune checkpoint inhibitors (ICIs).
Methods We utilized real-world clinical and transcriptomic data collected under the Total Cancer Care Protocol (NCT03977402) and Avatar® project within the Oncology Research Information Exchange Network (ORIEN) of 18 cancer centers to which all included subjects provided a written informed consent at their participating institutions. The immunoscore for each patient was calculated based on the estimated densities of tumor CD3+ and CD8+ T cells (Galon, 2020) utilizing CIBERSORTx and the LM22 gene signature matrix. Overall survival (OS) predictions were assessed using Harrell’s concordance index (C-index). Kaplan-Meier (KM) curves and the log-rank test were used to assess the immunoscore ability to stratify risk groups.
Results Patients (n=522) with 4 cancer types including melanoma (n=125), renal cell carcinoma (n=149), non-small cell lung cancer (n=128) and head and neck cancer (n=120) treated with 6 immune checkpoint inhibitor (ICI) regimens were included in this analysis. ICI regimens were nivolumab (n=219), pembrolizumab (n=202), ipilimumab+nivolumab (n=69), ipilimumab (n=30), avelumab (n=1) and cemiplimab (n=1). Table 1 summarizes the overall C-index and associated 95% CIs and log-rank p values for the entire cohort resulting from estimated immunocore categorizations. KM analyses of the entire cohort are displayed in figure 1. We compared the performance of the immunoscore as a prognostic biomarker in the 4 cancer types, with significant results seen only in the melanoma and head and neck cancer cohorts (table 2, figure 2).
Conclusions The CD3+, CD8+ T Cell immunocore estimated from transcriptomic data represents a prognostic biomarker for estimating overall survival in patients with metastatic melanoma and head and neck cancer treated with ICIs in a real-world setting and can be used as a reference in prognostic biomarker development. Integration with other biomarker candidates that may guide the choice of ICI regimen (anti-PD1 monotherapy versus combinations) is underway.
Acknowledgements We are grateful to the participating patients and their family members as well as all research staff supporting the conduct of the Total Cancer Care protocol.
Trial Registration NCT03977402
Ethics Approval We utilized real-world clinical and transcriptomic data collected under the Total Cancer Care Protocol (NCT03977402) and Avatar® project within the Oncology Research Information Exchange Network (ORIEN) of 18 cancer centers to which all included subjects provided an IRB-approved written informed consent at their participating institutions.
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