Purpose: CD19-specific chimeric antigen receptor (CAR) T-cell therapy is effective against refractory or relapsed (R/R) B-cell lymphoma, but the efficacy is hindered by the existence of PD-1/PD-L1 pathway. Patients and Methods: Here, we generated a novel anti-CD19 CAR-expressing PD-1/CD28 chimeric switch-receptor (CD19-PD-1/CD28-CAR). We then conducted a phase Ib study to evaluate safety and efficacy of CD19-PD-1/CD28-CAR T cells in the treatment of PD-L1+ B-cell lymphoma. Results: We found that CD19-PD-1/CD28-CAR T cells had superior T-cell proliferation, cytokine production, and sequentially capability of killing PD-L1+ B-cell lymphoma cells in vitro and in vivo relative to the prototype, CD19-CAR T cells. Among 17 adult patients with R/R lymphoma who received the CAR T therapy, 10 patients had objective response (58.8%), including seven patients with complete remission (41.2%). At a median follow-up 15 months, median overall survival for all patients was not reached. Remarkably, no severe neurologic toxicity or cytokine release syndrome was observed. Conclusions: This first-in-human study demonstrates the tolerability, safety, and encouraging efficacy of CD19-PD-1/CD28-CART in PD-L1+ large B-cell lymphoma.

SUMMARY BackgroundCarbon dioxide (CO 2 ) insufflation has been proposed as an alternative to air insufflation to distend the lumen in gastrointestinal (GI) endoscopy.

T cells recognize antigen fragments from proteolytic products that are presented to them in the form of peptides on major histocompatibility complex (MHC) molecules, which is crucial for the T cell to identify infected or transformed cells. Autophagy, a process that delivers cytoplasmic constituents for lysosomal degradation, has been observed to provide a substantial source of intra- and extracellular antigens for MHC presentation to T cells, which will impact the tumor-specific immune response. Meanwhile, extracellular components are transported to cytoplasm for the degradation/secretion process by the endo-/exosomal pathway and are thus involved in multiple physiological and pathological processes, including immune responses. Autophagy and endo-/exosomal pathways are intertwined in a highly intricate manner and both are closely involved in antigen processing for MHC presentation; thus, we propose that they may coordinate in antigen processing and presentation in anticancer T cell immune responses. In this article, we discuss the molecular and functional crosstalk between autophagy and endo-/exosomal pathways and their contributions to antigen processing for MHC presentation in anticancer T cell immune responses.

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GNRI is not an independent predictor for DLBCL patients.