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Cancer Immunology Research

Cancer Immunology Research, launched in 2013 with Glenn Dranoff as founding Editor-in-Chief, is published by the AACR. The Journal illuminates the interplay between tumors and the immune system, with Robert D. Schreiber and Philip D. Greenberg serving as the Editors-in-Chief.

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Rational protein design yielded a CD20 CAR that outperforms a clinically relevant CD19 CAR in lymphoma models, providing a new candidate for non-Hodgkin lymphoma therapy. This protein-engineering approach could be applied to develop additional CARs against diverse antigens.

The authors find a correlation between abundance of self-renewing CD8+ T cells in blood and response of cancer patients to PD-1 blockade, suggesting assessment of T-cell regenerative status might serve as a noninvasive, predictive biomarker of immunotherapy response.

Research Articles

NKT cells employ an undefined mechanism to undergo central memory–like differentiation, which is associated with increased antitumor potential. The authors demonstrate that LEF1 drives central memory programming in human NKTs, informing rational design of NKT-based cancer immunotherapy.

A combination of naked mRNAs encoding IL12 and IL18 is efficacious upon intratumoral injection but is toxic if lipo-formulated and given systemically. A nonrepressible IL18 mutant markedly increases local abundance of IFNγ and enhances immunotherapeutic efficacy.

circATP2B4 is found to be associated with the development and progression of epithelial ovarian cancer. Extracellular vesicle-packaged circATP2B4 induces macrophage M2 polarization and cancer cell metastasis via SREBF1/PI3Kα/AKT signaling, suggesting a role as a diagnostic and therapeutic target.

In mice with checkpoint-refractory melanoma, antigen-loaded EVs induce antitumor immune responses. Prophylactic immunization with EVs sensitizes tumors to anti–PD-L1 and leads to prolonged survival, indicating potential use of EVs against checkpoint-refractory cancers.

Small extracellular vesicles containing PD-L1 secreted by tumor cells can inhibit host immunity, preventing tumor cell killing. HRS is identified as a regulator of PD-L1+ small extracellular vesicle secretion, therefore presenting a potential target for enhancing immunotherapy.

The authors show that tumor or host CMTM6 deficiency can promote cytotoxicity-dependent antitumor immune responses, even in the absence of the PD-1/PD-L1 axis. The data suggest CMTM6 as a novel target for oncoimmunology gene therapy and combination treatment.

A therapeutic HPV16 vaccine consisting of E1, E2, E6 and E7 viral antigens delivered by adenoviral vectors is shown to suppress the growth of HPV16-positive transplanted tumors in mice, especially when used together with cisplatin.

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