Genomic expression of MSR1 in solid tumors associates with response to anti-PD1 and anti-CTLA4 therapies

Abstract Immuno-oncology has gained momentum with the approval of antibodies that have demonstrated clinical activity in different indications. Unfortunately, for anti PD (L)1 agents in monotherapyonly half of the treated population will achieve a clinical response. For other agents like anti-CTLA4 antibodies, no biomarker exists, and tolerability can limit the administration of this compound. In this study, using publicly available genomic datasets, we evaluated the expression of the macrophage scavenger receptor-A (SR-A) ( MSR1) and its association with response to check point inhibitors (CPI). MSR1 was mainly and differently expressed in GBM, PAAD, ESCA, STAD, SKCM, OV, KIRC, THYM, HNSC and BRCA, within the tumor microenvironment. MSR1 was associated with the presence of macrophages, dendritic cells (DCs) and neutrophils in most of the studied indications. The presence of MSR1 was associated with macrophages with a pro-tumoral or M2 phenotype and correlated with TIM3 expression. MSR1 predicted favorable overall survival in patients treated with anti-PD1 (HR: 0.56, FDR: 1%, p = 2.6e-05); anti PD-L1 (HR: 0.66, FDR:20%, p = 0.00098) and anti-CTLA4 (HR: 0.37, FDR:1%, p = 4.8e-05). When studying specifically skin cutaneous melanoma (SKCM), we observed a similar effect: anti-PD1 (HR: 0.65, FDR: 50%, p = 0.0072); and anti-CTLA4 (HR: 0.35, FDR:1%, p = 4.1e-05). In a different dataset of SKCM patients, expression of MSR1 predicted clinical response to anti-CTLA4 (AUC: 0.61, p = 2.9e-02). In conclusion, we described the expression of MSR1 in some solid tumors and its association with innate cells and M2 phenotype macrophages. Of note, MSR1 presence predicted response to CPI particularly anti-CTLA4 therapies in different cohorts of patients. Future studies should prospectively explore the association of MSR1 expression and response to anti-CTLA4 strategies in solid tumors.