Decoding the Immune Microenvironment of Secondary Chronic Myelomonocytic Leukemia due to DLBCL with CD19 CAR-T Failure by Single-cell RNA-seq

Multiple studies have confirmed the occurrence of second tumors as a rare incidence of CAR-T therapy, but one of the complications that does warrant in-depth exploration. According, given the relatively small number of reported second tumor types thus far, additional comprehensive occurrence and characterization of a new second tumor type after CAR-T therapy remains essential for understanding the risk of potential tumors with this therapy, as well as for defining the role of immune microenvironment in malignant transformation. In this article, a new second tumor type CMML was identified in a patient who had received CD19 CAR-T therapy for DLBCL. The immune microenvironment of both the pre- and post-treatment of secondary CMML and primary CMML were deeply profiled by ScRNA-seq. Our results demonstrated an enhanced inflammatory cytokines, chemokines, and immunosuppression state of monocytes/macrophages, which may inhibit the cytotoxicity of T/NKs in secondary CMML. In contrast, the cytotoxicity of T/NKs were enhanced in secondary CMML after treatment. Collectively, our results highlight a new type of second tumor, CMML after CAR-T therapy and provide a framework for defining the immune microenvironment of second tumor occurrence after CAR-T therapy. Our results also provide a rationale for targeting macrophages to strengthen CMML treatment.