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Hematological malignancies are one of the most lethal illnesses that seriously threaten human life and health. Lipids are important constituents of various biological membranes and substances for energy storage and cell signaling. Furthermore, lipids are critical in the normal physiological activities of cells. In the process of the lethal transformation of hematological malignancies, lipid metabolism reprogramming meets the material and energy requirements of rapidly proliferating and dividing tumor cells. A large number of studies have shown that dysregulated lipid metabolism, commonly occurs in hematological malignancies, mediating the proliferation, growth, migration, invasion, apoptosis, drug resistance and immune escape of tumor cells. Targeting the lipid metabolism pathway of hematological malignancies has become an effective therapeutic approach. This article reviews the oncogenic mechanisms of lipid metabolism reprogramming in hematological malignancies, including fatty acid, cholesterol and phospholipid metabolism, thereby offering an insight into targeting lipid metabolism in the treatment of hematological malignancies.

Purpose: CD7 CAR-T therapy has potent antitumor activity against R/R T-ALL/LBL, however, immune reconstitution post CAR-T remains largely unknown. Experimental Design: An open-label phase I clinical trial (ChiCTR2200058969) was initiated to evaluate safety and efficacy of donor-derived CD7 CAR-T cells in seven R/R T-ALL/LBL patients. CAR-T cells were detected by flow cytometry and PCR. Cytokine levels were quantified by cytometric bead arrays. ScRNA-seq was adopted to profile immune reconstitution. Results: Optimal CR was 100% on day 28, and median followed-up time was four months. Leukopenia, thrombocytopenia, and neutropenia were observed in six patients, and infections occurred in five patients. Two patients died of serious infection and one died of a brain hemorrhage. CAR-T cells expanded efficiently in all patients. CD7+ T cells were eliminated in peripheral blood on day 11 after infusion, and CD7- T cells dramatically expanded in all patients. ScRNA-seq suggested that immunological activities of CD7- T cells were stronger than those of T cells before infusion due to higher expression levels of T-cell function-related pathways, and major characters of such CD7- T cells were activation of autoimmune-related pathways. Monocyte loss was found in two patients who died of serious infections, indicating the main cause of the infections after infusion. S100A8 and S100A9 were identified as potential relapse markers due to their notable upregulation in leukocyte lineage in relapsed patients versus non-relapse controls. Conclusions: Our data revealed cellular level dynamics of immune homeostasis of CD7 CAR-T therapy, which is valuable for optimizing the treatment of R/R T-ALL/LBL.