Association of CD8 T cell infiltration in the tumor microenvironment with survival outcomes in patients with metastatic renal cell carcinoma (mRCC).
Authors: Goswamy Rohit Vivek , Yildirim Ahmet , Wei Mengting , Liu Yuan , Choi Yujin , Brown Jacqueline T , Nazha Bassel , Master Viraj A. , Martini Dylan J. , Carthon Bradley Curtis , Harris Wayne Bernard , Kucuk Omer , Kissick Haydn , Hartman Caitlin , McClintock Greta Russler , Vo Baohan Thi , Jansen Caroline Stewart , Zhuang Tony , Bilen Mehmet Asim 
Published: June 2024

e16527

Background: Recent data have reported CD8 T cell infiltration into the intratumoral environment has been associated with favorable clinical outcomes in those patients who had tumor resection months/years prior to metastatic diagnosis and systemic therapy. We hypothesize that mRCC patients studied at our institution will display similar improved overall survival (OS) and progression free survival (PFS) in those with higher CD8 T cell infiltration. Methods: We conducted a retrospective analysis of patients with mRCC treated at Winship Cancer Institute between 1/1/2018 and 8/31/23. Overall survival (OS) and progression-free survival (PFS) were defined as months from treatment initiation to death or clinical/radiographic progression, respectively. The correlation between CD8 T cell infiltration and OS/PFS was studied in 39 patients diagnosed with metastatic RCC under systemic therapy. We used immunofluorescence (IF) imaging and flow cytometry to investigate how intratumoral T cells in patients’ tumors (resected months/years prior to receiving checkpoint therapy) predicted patient outcomes after immunotherapy. CD8 T cell infiltration was calculated as a proportion of T cells relative to other mononuclear cells within the tumor microenvironment. The groups were divided into high expressors of CD8 T cells (>0.79% CD8 T cell infiltration) or low expressors of CD8 T cells (< 0.79% CD 8 T cell infiltration). Univariate (UVA) analysis was carried out for OS and PFS using Cox proportional hazard model. Results: A total of 39 eligible patients were included with a median follow up of 60 months. Median age was 64 years (range = 38-77), 62% were male, 38% were female, and 80% had clear cell histology. 36% received checkpoint inhibitor (CPI) monotherapy, 28% received combination CPI, and 26% received CPI in combination with tyrosine kinase inhibitor (TKI). 4% received other therapies. Patients with higher CD8 T cell infiltration had improved OS and PFS outcomes on Kaplan Meier analysis (>0.79% T cell infiltration - OS at 60 months 35.2% [95% CI 14.7-56.6%], PFS at 60 months 25.6% [95% CI 9.7-45.1%]; <0.79% T cell infiltration - OS at 60 months 11.8% [95% CI 2.0-31.2%], PFS at 60 months 5.9% [95% CI 0.4-23.5%]. For those patients with CD8 T cell infiltration <0.79%, the hazard ratio for OS was 2.42 (1.21-4.85; 95% confidence interval; P-value 0.012). For those patients with CD8 T cell infiltration <0.79%, the hazard ratio for PFS was 2.22 (1.07-4.63; 95% confidence interval; P-value 0.033). Conclusions: This work furthers our understanding of the tumor environment in those patients who previously received surgical resection but progressed to metastatic disease. CD8 T cells in tumor environment are an important predictor of objective clinical response to CPI therapy. Further work needs to be done in larger, prospective trials to confirm these findings.