KRT17 is highly expressed in deficient mismatch repair colorectal cancer, where it promotes T-cell infiltration via the YTHDF2–CXCL10 axis. KRT17 expression correlates with improved immunotherapy responsiveness, highlighting a potential prospective biomarker and therapeutic target for immunotherapy.

Resistance to immune checkpoint inhibitors can be caused by IFNγ signaling pathway defects. The authors show that such resistance can be primarily caused by reduced MHC-I expression and that this can be overcome by NF-κB–targeted therapies.

A novel role for the MYC proto-oncogene is revealed, and its contribution to immunotherapy resistance is demonstrated. Mechanistically, MYC inhibits IFNγ signaling through JAK2 downregulation, paving the way for innovative combinations of immunotherapy with MYC-targeting therapies.

Feasibility and safety of a personalized adoptive cell therapy (ACT) against multiple peptide–HLA cancer targets is demonstrated. Results warrant further investigation regarding the use of multi-targeted ACT approaches with high-avidity TCR products in patients with advanced metastatic cancer.

Some B-NHL patients relapse following CAR T-cell therapy. The authors show CD20xCD22 dual allogeneic CAR T cells could address mechanisms of resistance, including tumor antigen escape or heterogeneous expression, while reducing manufacturing complexity and, thus, benefit B-NHL patients.

The Authors identify an IL-12 prodrug that is selectively activated in the tumor microenvironment and generates potent antitumor immunity in mice by activating and restoring the metabolic health of tumor-infiltrating lymphocytes while preventing toxicity associated with systemic IL-12.

Preactivating γδT cells using a cytokine combination enhances their antitumor efficacy as an adoptive cell therapy. Transfer of the preactivated cells additionally induces endogenous CD8⁺ T-cell responses and sensitizes tumors to anti–PD-L1, highlighting a potential combinational strategy.

The authors report the mechanisms underlying the ability of the IL2/IL15 mimetic NL-201 to stimulate inflammation in ‘cold’ tumors and drive antitumor efficacy in a manner that is cooperative with PD-1 inhibition, highlighting its potential for clinical translation.

CD8⁺ T-cell states and clonal architecture are characterized in a real-life, representative cohort of patients with acute myeloid leukemia. A differentiation and clonal expansion gradient from healthy to relapsed/refractory is identified, which is predictive of patient outcomes.