Abstract 3308: Predictive biomarkers of response to immune checkpoint inhibitors in metastatic renal cell carcinoma

Abstract

Abstract Background: Since the introduction of Immune checkpoint inhibitors (ICIs) combination therapy to renal cancer treatment, it has revolutionized the treatment of renal cancer, with many reports of excellent therapeutic effects. However, it is not known which patients will benefit the most. Materials and methods: PBMC(Peripheral Blood Mononuclear Cells)samples were collected prospectively from patients with advanced and metastatic renal cell carcinoma (RCC) prior to initiation of ICI treatment (baseline) and 2 or 3 weeks after the first cycle of ICI treatment (post-dose 1). We collected PBMCs from 24 patients with a cell count of more than 50,000 were analyzed using antibodies that distinguishCD4 and CD8 cells including Effector, Memory cells population, B cells, Monocyte, NK(Natural Killer) cells, MDSC(Myeloid-Derived Suppressor Cells ), DC(Dendritic cells), CD4 (Th1, Th2, Th17, Tfh), Immune checkpoint molecules including CD223 (LAG3), CD279 (PD1), TIM3, CD152 (CTLA4), CD278 (ICOS), FOXP3. Results: First, we compared the Fold Change (FC) before and after drug administration in the group that did not respond to treatment (SD: Stable Disease or PD: Progressive disease) and the group that did respond to treatment (PR: Partial Response, CR: Complete Response). The results showed that CD4 positive cells (non-responder Median 0.79 vs responder Median 1.64, p=0.0317, respectively), monocytes: CD56-HLADR+ (non-responder Median 0.87 vs responder Median 1.20, p=0.0159, respectively), but not in other cell populations.Next, we compared the groups that did and did not respond to treatment before and after treatment. We could not identify any biomarker cell population before treatment, the number of CD4 Effector cells (CD4+CD45RO-CD197-) was significantly higher in the post-treatment (PD1) group (PR or CR) than in the non-treatment group (SD or PD). (p=0.0303, respectively) Conclusion: Elevation of CD4 positive cells and monocytes (CD56-HLADR+) before and after treatment and the number of CD4 Effector cells (CD4+CD45RO-CD197-) after treatment may be biomarkers of treatment response. Citation Format: Takanobu Motoshima, Yuji Miura, Toshiki Amami, Shigeyasu Kitano, Masaya Baba, Tomomi Kamba. Predictive biomarkers of response to immune checkpoint inhibitors in metastatic renal cell carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3308.