Flt3L-derived cDC1 are demonstrated to be superior to GM-CSF–generated DCs as a cell-based vaccine. Flt3L-cDC1 acquire tumor antigen, migrate to tumor-draining lymph nodes, and directly prime antitumor T-cell responses, highlighting their potential as a cancer therapeutic.

The authors have established a library of human mutant p53–reactive T-cell receptors potentially useful for the treatment of 7.3% of patients with cancer and show one metastatic breast cancer patient responding to such therapy.

Generating antitumor immunity via innate immune signaling represents an emerging therapeutic strategy. Functional profiling of human mesothelioma tumor explants expressing elevated STING uncovers distinct consequences of STING agonism that support combining such treatment with NK cell–based therapies.

CAR T cells expressing Super2 and IL-33 are shown to promote antitumor immunity in multiple solid tumor models and to overcome antigen loss, suggesting this could be a universal CAR T-cell platform for treatment of solid tumors.

VAX014 is an early-stage oncolytic agent undergoing clinical testing for bladder cancer. Combinationwith anti–PD-L1 leads to enhanced antitumor responses, generation of immunologic memory, and abscopal effects, suggesting clinical utility of this combination for advanced bladder cancer.

The authors describe immunologic features within melanoma brain metastases in response to immune checkpoint inhibition, and identify relationships between T-cell distribution, phenotype, and clonotype across the brain and blood that have the potential to influence clinical decision-making.

Novel preclinical models of immune checkpoint inhibitor resistance improve our understanding of heterogeneous clinical phenotypes and efficacy of combination regimens. Overexpression of pigment epithelium derived factor by murine tumor cells contributes to resistance to immune checkpoint inhibitors.

KDM5A is shown to suppress CD8⁺ T-cell infiltration into tumors by inhibiting the antigen processing and presentation pathway. The results suggest KDM5A as a promising epigenetic target for boosting antitumor immunity.