Introduction: The recent success of anti-PD1 therapeutics is known to be associated with an upregulated Th1 gene signature and an immunogenic tumor microenvironment (TME). There remains a crucial need for predictive biomarkers to direct immunotherapy in patients with metastatic renal cell carcinoma (mRCC). We sought to evaluate the association of Th1 marker T-bet with response to immunotherapy in patients with mRCC.
Methods: We examined the tumors of 26 patients with mRCC who received immunotherapy. Using quantitative immunofluorescence, we assessed T-bet T lymphocyte density within the tumor and TME. Patients were stratified by T-bet density. Kaplan-Meier analysis and log rank tests were used to assess differences in survival from the date of first immunotherapy treatment.
Results: Patients with a high density of T-bet positive T cells within the TME, particularly at the tumor-parenchymal interface, had prolonged survival after receiving immunotherapy (p = 0.019). The mean survival of patients with high T-bet density was > 144 months vs. 46.7 months in patients with low T-bet density. There was no association between outcome and intratumoral T-bet staining (p = 0.133).
Conclusions: In patients with mRCC, a high density of T-bet positive T lymphocytes at the tumor-parenchymal interface was associated with a favorable response to immunotherapy. Immunofluorescent quantification of T-bet positive T cells may prove to be an accurate tool to recapitulate a pre-existing Th1 antitumor response that can be invigorated by anti-PD1 treatment. Source of
Funding: Urology Care Foundation Research Scholar Award Program; Society for Urologic Oncology