Immune microenvironment and its influence on CAR-T treatment outcomes in B-NHL

B-cell non-Hodgkin's lymphoma (B-NHL) is a highly heterogeneous tumor. Currently, CAR-T cells have been widely used in the treatment of B-cell lymphomas, with a complete response rate reaching 40%-60%. More and more studies have shown that the immune microenvironment plays an important role in the occurrence and development of B-NHL. However, it is still unclear what role the tumor microenvironment plays in the effect of CAR-T therapy on B-NHL. We analyzed the components of 44 tumor tissue biopsy samples from 36 patients with relapsed or refractory Diffuse large B-cell lymphoma (R/R DLBCL) in our center to explore the immune cell components in the tumor microenvironment that correlated with improved clinical outcomes of CAR-T therapy. The median follow-up time was 8.5 months. We analyzed the impact of various cells on patient survival and identified multiple prognostic protective factors and risk factors. Among them, Treg cells (P < 0.009; HR = 0.32) are a key prognostic protective factor that associated with the efficacy of CAR-T therapy. Further analysis of tumor biopsy samples before and after CAR-T treatment in the same patients revealed that higher Treg cells were associated with the better CAR-T efficacy and were associated with sustained CAR-T persistence. There were more Treg cells in biopsy samples without CAR-T cells remaining after CAR-T treatment. The overall response rate in non-residual CAR-T cells group was 61.5% (n = 8), consisting of CR (30.8%, n = 4), PR (30.8%, n = 4), SD (7.7%, n = 1), and PD (30.8%, n = 4) compared to the residual CAR-T cells group (PR: n = 1, 25%).