A Sampling of Highlights from the Literature: Article Recommendations from Our Deputy and Senior Editors

A therapeutic peptide vaccine yielded a 25% ORR for patients with fibrolamellar hepatocellular carcinoma (from Nephron via Wikimedia Commons).Given that the DNAJ-PKAc chimeric protein that drives fibrolamellar hepatocellular carcinoma is immunogenic, Baretti and colleagues conducted a phase I clinical trial of a DNAJ-PKAc–targeting therapeutic peptide vaccine in combination with nivolumab and ipilimumab. Among the 12 patients who completed vaccine priming and were evaluable for both immunological and clinical endpoints, the overall response rate was 25%. DNAJ-PKAc–specific T-cell responses were detectable after vaccination in the peripheral blood of nine of these patients, including the three responders. Two of the responders eventually had disease progression, with resistance driven by T-cell exhaustion. These preliminary data support further investigation of this therapeutic approach.Baretti M, …, Yarchoan M. Nat Med 2025 Nov 24;31,4246–4255.Tregs can both promote and limit colorectal cancer growth (From NIAID via Wikimedia Commons).Regulatory T cells (Tregs) are associated with poor prognosis in many solid tumors, but in colorectal cancer (CRC), they are associated with better patient outcomes. Using an orthotopic mouse model of microsatellite stable CRC and human samples, Huang and colleagues identify two Treg subsets, IL10+ and IL10−, with opposing functions. IL10+ Tregs are antitumoral as they limit IL17 production by CD4+ T cells, whereas IL10− Tregs are protumoral. Consistent with this, depletion of IL10+ and IL10− Tregs in the mouse model increases and decreases tumor growth, respectively, suggesting the need for selective therapeutic targeting of Treg subsets.Huang X, …, Rudensky AY. Immunity 2026 Jan 13;59,145–160.E9.Neutrophils can enhance the effects of CAR T cells (from NIAID via Wikimedia Commons).The immunosuppressive tumor microenvironment, as well as antigen heterogeneity, hinder chimeric antigen receptor (CAR) T-cell effectiveness against solid tumors. Zuo and colleagues find that engaging neutrophils can enhance the therapeutic efficacy of CAR T-cell therapy in preclinical models of small cell lung cancer and melanoma. Administration of IL36γ armored CAR T cells without lymphodepletion eradicates tumors in these models. This is because the IL36γ armored CAR T cells induce recruitment and reprograming of neutrophils into antigen-presenting and tumoricidal states, which in turn activates endogenous antitumor T-cell responses by antigen spreading. This approach could be extended to other adoptive cell therapies for solid tumors.Zuo Y, …, Brentjens RJ. Cancer Cell 2025 Dec 11;DOI:10.1016/j.ccell.2025.11.007.Dietary restriction of calorie intake slows tumor growth via immune mechanisms (from rawpixel.com).Dietary restriction of calorie intake slows tumor growth. Two studies identify immune mechanisms underlying this effect. Oswald and colleagues find that dietary restriction promotes effector T-cell expansion and limits terminal T-cell exhaustion. This is driven by an increase in circulating ketone body levels, which enhances TCA cycle metabolism and mitochondrial bioenergetics of CD8+ T cells, and thereby promotes their effector function. Gao and colleagues find that caloric restriction modulates the profile of tumor-infiltrating neutrophils, reducing their levels of the protein hypoxia-inducible lipid droplet-associated (HILPDA). Low HILPDA decreases transfer of lipids from neutrophils to immune effector cells, an event that would impair effector-cell cytotoxicity. Future studies will look to harness the new knowledge therapeutically.Oswald BM, …, Jones RG. Nat Metab 2025 Dec 09;7,2489–2509.Gao J, …, Gan Y. Cell Metab 2025 Dec 05;DOI:10.1016/j.cmet.2025.11.007.Melanosomes can promote immune evasion by melanoma (From Laboratoires Servier via Wikimedia Commons).Not all melanomas are responsive to immunotherapy. Chemla and colleagues provide new insight into the mechanisms underlying this, finding that melanosomes, which are large extracellular vesicles secreted by melanocytes, display MHC molecules and carry tumor-associated antigens. Melanosomes bearing MHC-bound tumor-associated antigens compete with tumor cells for binding to T-cell receptors on tumor-infiltrating CD8+ T cells, thereby serving as decoys that prevent CD8+ T cells from being properly activated to clear the tumor. Inhibiting melanosome release in preclinical models increases CD8+ T-cell infiltration and reduces tumor immune evasion, supporting melanosome inhibition as a potential strategy to improve immune responses against melanoma.Chemla Y, …, Levy C. Cell 2025 Dec 15;189,233–251.e29.CCR7+ DCs modulate immune activation and suppression in the tumor microenvironment (from A. Rad via Wikimedia Commons).The factors regulating the function of intratumoral dendritic cells (DCs), which are critical for effective antitumor immunity, are incompletely characterized. Zitti and colleagues find that the intratumoral location of CCR7+ DCs influences antitumor immunity in human cancers and mouse models. CCR7+ DCs are recruited by fibroblast-derived CCL19 to perivascular niches, where they promote T-cell activation and antitumor activity. Regulatory T cells (Treg) are often present in these niches. Anti–PD-1 therapy not only enhances perivascular clustering of CCR7+ DCs and antitumor activity, but also prolongs CCR7+ DC–Treg interactions. The data provide new insight into the balance between immune activation and suppression in the tumor microenvironment.Zitti B, …, Pittet MJ. Immunity 2026 Jan 13;59,161–176.E12.