Abstract 6380: Essential chemokine score as a potential surrogate for immune checkpoint therapy in pan cancer

Abstract

Abstract The inhibition of the immune checkpoint axis of programmed cell death 1 (PD-1) and PD-1 ligand 1 (PD-L1) has achieved significant anti-tumor therapeutic success, though it is still inadequate to ameliorate the dismal outcomes of the majority of cancer patients. Therefore, it is urgent and of interest in scrutinizing predictive indicators to enable a precision anti-tumor strategy, predict the therapeutic response, and better comprehend the mechanisms of resistance to immunotherapies. To evaluate the vigorous potential of CXCL9/10/11 score as a single, universal, and reliable surrogate to predict the response to anti-PD-1 therapy in different cancer types. The analyses in this study used the cancer genomic data from 31 different solid cancers in the Cancer Genome Atlas (TCGA) to calculate the CXCL9/10/11 score, CD274 expression, tumor mutational burden (TMB), and tumor immune phenotypes (IPs). The difference of CD274 expression, TMB, and tumor IPs was then compared between CXCL9/10/11 scoreLow and scoreHigh groups for each cancer type. Furthermore, this score was examined in two cohorts of patients with different cancer types treated with anti-PD-1 therapy to predict the expression of CD274, regression/progression status, and progression-free survival (PFS) between the scoreLow and scoreHigh groups. CD274 expression, TMB, and most tumor IPs were significantly elevated in CXCL9/10/11 scoreHigh group than in the scoreLow group among 12 different TCGA cancer types including breast cancer, lung cancer, colon cancer, melanoma, bladder cancer, and endometrial cancers. In two validation cohorts of 49 patients with lung cancer, melanoma, and head and neck cancer, and 85 patients with metastatic melanoma treated by anti-PD-1 therapy, respectively, scoreHigh tumors exhibited significantly high expression of CD274 than scoreLow tumors (p = 0.0006 and p = 0.0023, respectively). Significantly more patients in the scoreHigh group achieved post-treatment cancer regression than those patients in the scoreLow group (p = 0.0200 and p = 0.0427, respectively). The patients in the scoreHigh group enjoyed a significantly longer PFS than those in the scoreLow group (p = 0.0179 and p = 0.0229, respectively). Our findings suggest that CXCL9/10/11 score can serve as a single, universal, and reliable surrogate corresponding to CD274 expression, TMB, and tumor IPs within one variable among many different cancer types, and exhibits a vigorous and attractive potential to predict the therapeutic response to anti-PD-1 therapy in patients. Citation Format: Xuhui Bao, Liyi Xie. Essential chemokine score as a potential surrogate for immune checkpoint therapy in pan cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 6380.