The authors report that combined PD-1 and Ang1/2 blockade was largely ineffective in a clinical trial. Durable responses in two patients with left-sided microsatellite stable CRCs harboring ERBB2 amplification, without baseline liver metastases, were observed.

B-cell maturation antigen (BCMA) is expressed in multiple myeloma and is a candidate for multiple myeloma–targeting CAR T-cell therapy. This study demonstrates that integrating CD27 costimulation improves the efficacy of BCMA CAR T-cell therapy for multiple myeloma.

The authors report the preclinical development of TAC01-CLDN18.2 for the treatment of Claudin 18.2-positive solid tumors. TAC01-CLDN18.2 is an autologous T-cell therapy that capitalizes on signaling through the endogenous TCR for efficacious and safe antitumor responses.

Genetic deletion of EZH2 is detrimental to T-cell function. In contrast, the authors show that transient EZH2 inhibition during T-cell activation prior to the phenotypic onset of exhaustion enhances T-cell function in the context of adoptive T-cell therapy.

Glutamine metabolism affects cancer cell growth. The authors show that long-term glutamine blockade in bladder cancer induces PD-L1–mediated immunosuppression. Combination therapy of JHU083 and gefitinib reverses PD-L1 upregulation, alleviating immunosuppression and leading to enhanced antitumor effects.

Predicting which tumor neoantigens are most relevant for tumor regression has proven difficult. The authors show that expression level can modulate a neoantigen’s tumor rejection capacity, information critical for developing neoantigen-based cancer immunotherapies.

β2M- or TAP-deficient cancer cells are thought to evade CD8⁺ T cells. The authors show that this is not always the case. In TAP1-KO cells, Sec62 facilitates peptide entry into the ER for MHC I loading.

The radio-induced antitumor immune response is an important contributor to the success of radiotherapy. We show that myeloid deletion of Trim33 induces IFNβ expression and is a potential target to better understand immune responses to radiotherapy.

This study identifies complement factor H as a ligand for the immune checkpoint molecule ICOS, which impacts Treg function in glioma. Targeting FH could improve immunotherapy, offering new strategies for treating this immunosuppressive cancer.

This study identified a subset of exhausted tumor-infiltrating NK cells that express CD49a. Blockade of CD49a resulted in antitumor activity when used alone or in combination with anti–PD-L1, mainly in an NK cell–dependent manner.