T-Cell Receptor (TCR) repertoire as predictive biomarker of immune checkpoint inhibitor (ICI) response: a study on baseline features and dynamic evolution across multiple cancer types

Immune checkpoint inhibitors (ICIs) have revolutionized oncology. However, we still lack robust predictive biomarkers. Peripheral blood analysis is a non- invasive method to collect biomarkers. Inflammation scores such as NLR and dNLR are easily assessable and non-expansive, while some data suggest a correlation between development of immune-related adverse events (irAEs) and response to ICIs. Lastly, T-cell receptor (TCR) repertoire is a promising biomarker. From the systematic review we performed, high diversity at baseline and an increase in clonality and after treatment appear to be predictors of response to ICIs.Primary objective of this study was to assess correlations of TCR repertoire with tumor response to anti-PD1/PD-L1. Secondary endpoints were correlation between inflammation scores, irAEs and response. Because of samples conservation issues, we were unable to perform TCR analysis. We therefore focused on the secondary objectives of the study.26 patients were included in our study. Patients developing irAEs of any grade showed higher neutrophile-lymphocyte ratio (NLR) and derived-NLR (dNLR) scores in patients receiving ICI as monotherapy. After Receiver Operator Characteristic (ROC) analysis, both appeared to be good predictors of irAEs, with an area under the curve (AUC) 0.93 and 0.90, and optimal thresholds of 2.42 and 1.34, respectively. However, only for NLR relative-risk (RR) analysis achieved statistical significance (RR 7.00, p 0.035).We also observed a significantly higher RR of objective response rate (ORR), disease control rate (DCR) and durable clinical benefit (DCB) in patients experiencing irAEs that required steroids administration or treatment interruption both in the overall population and in multiple subgroups (RR ranging from 1.33 to 4.50, p ranging from 0.001 to 0.5). Median progression- free survival (PFS) in the overall population was significantly higher among these patients (mPFS 17.14 vs 5.36 months, hazard ratio (HR) 0.262, p value 0.048 and mPFS 17.14 vs 5.36 months, HR 0.160, p 0.041, respectively), while median overall survival (OS) was significant only for patients needing treatment interruption (mOS not reached (NR) vs 7.57 months, HR not estimable, p value 0.034).In conclusion, we collected interesting data on the predictive role of NLR and dNLR, as well as of irAEs occurrence, that we expect to validate in future, larger studies, focused on patients treated with ICI monotherapy.