Mechanisms of resistance to TIL-ACT are ill-defined. The authors report that transfer of TILs caused immune selection of a resistant melanoma cell clone in one patient. T-cell collection from multiple tumor sites could help overcome this issue.

The role of IL3 in antitumor immunity is ill-defined. The authors reveal that IL3 mediates crosstalk between CTLs and IL4-producing basophils, rejuvenating CTLs and amplifying their antitumor ability, suggesting new approaches to advance and optimize cancer immunotherapy.

The authors show that the piRNA piR-hsa-30937 in PNEN cell–derived small extracellular vesicles (sEV) promotes CD276 expression in macrophages to suppress T-cell immunity. The data indicate sEV piR-hsa-30937 and CD276 as potential immunotherapeutic targets in PNEN.

The authors show in myeloid-rich urologic tumors that glutamine antagonism in TAMs results in functional alterations including increased tumor-cell phagocytosis, inflammatory signaling, immune-proliferative pathways, and glycolysis. This promotes antitumor immunity, suggesting new therapeutic approaches for these immunotherapy-unresponsive tumors.

Immune-excluded tumors rarely respond to immunotherapy. The authors show that blocking interactions between the T-cell checkpoint PVRIG on TSCM and its ligand PVRL2 on intratumoral DCs induces T-cell proliferation and infiltration, suggesting new therapeutic opportunities for immune-excluded tumors.

The mechanisms underlying T_FH-cell differentiation in tumors are unclear. The authors show that SIRT3 triggers NAD⁺-dependent glycolysis and an mTOR–HIF1α–Bcl-6 pathway to reprogram T_FH-cell differentiation, which is meaningful for future immunotherapy approaches in cancer.

To address the pharmacokinetic challenges of traditional peptide-based cancer vaccines, the authors generate an engineered chimeric peptide–based orchestrated codelivery strategy, showing it enhances antitumor T-cell immunity. This approach may provide an avenue toward more effective cancer treatments.

In preclinical studies on the T-cell engager MP0533, the authors show that targeting multiple tumor-associated antigens may lead to better selectivity and efficacy in eliminating leukemic stem cells and blasts, representing a promising therapeutic strategy for AML.