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

CAR T cells targeting immunosuppressive macrophage reduce tumor growth (From Rawpixel.com).Two studies show that T cells expressing chimeric antigen receptors (CAR) targeting markers of immunosuppressive tumor-associated macrophages (TAMs), TREM2 and FOLR2, can eliminate these cells and control tumor growth. Yagel and colleagues show in two syngeneic models in humanized-TREM2 mice that TREM2-targeted CAR T cells engineered to secrete IL12 upon CAR activation remodel the tumor microenvironment (TME) to be antitumorigenic and elicit tumor regression without systemic toxicity. Mateus-Tique and colleagues show that CAR T cells targeting either TREM2 or FOLR2 and expressing low doses of IL12 remodel the TME, with loss of immunosuppressive TAMs and accumulation of CXCL9+ immunostimulatory macrophages, and cause tumor regression in multiple syngeneic cancer models.Yagel G, …, Amit I. Cancer Cell 2026 Jan 22;DOI:10.1016/j.ccell.2025.11.009.Mateus-Tique J, …, Brown BD. Cancer Cell 2026 Jan 22;DOI:10.1016/j.ccell.2025.12.021.Adding a selective anti–latent TGFβ1 to anti–PD-1 is safe and shows antitumor activity (from Emw via Wikimedia Commons).TGFβ1 contributes to resistance to immune checkpoint inhibitor therapy. In a phase I trial evaluating adding a selective anti–latent TGFβ1, linavonkibart, to the anti–PD-1 pembrolizumab, Yap and colleagues show that linavonkibart alone and together with pembrolizumab is safe and tolerable. In the expansion cohort of 78 patients with solid tumors nonresponsive to anti–PD-1, the confirmed objective response rate (ORR) is 20.0% for clear cell renal cell cancer, 18.2% for melanoma, and 9.1% for head and neck squamous cell cancer and urothelial cancer. Elevated baseline CD8+ T cells, regulatory T cells, and TGFB1 expression are associated with improved ORR, suggesting potential biomarkers for patient selection.Yap TA, …, Gan L. Nat Med 2026 Jan 13;DOI:10.1038/s41591-025-04157-w.Lymphatic vasculature in tumors is metabolically regulated (from NIAID via Wikimedia Commons).How lymphatic vessels can both help with antitumor responses and aid in metastasis is unclear. Karakousi and colleagues identify an inverse correlation between antitumor immune responses and intratumoral lymphatic abundance in mouse melanoma models and human melanoma samples. Deletion of the receptor for IFNγ in lymphatic endothelial cells expands the intratumoral lymphatic network, indicating that IFNγ inhibits intratumoral lymphangiogenesis. This occurs because IFNγ inhibits mitochondrial respiration, which prevents the emergence of a “tip-like lymphatic network” that can induce the formation of metastasis-supporting lymph node architecture. Limiting intratumoral lymphangiogenesis enhances response to immunotherapy, providing new insight into the importance of distinct lymphatic networks in determining therapeutic outcomes.Karakousi T, …, Lund AW. Cancer Cell 2026 Jan 22;DOI:10.1016/j.ccell.2025.12.019.BACH2 levels fine-tune T cells for adoptive-cell therapy (from Lemonedo via Wikimedia Commons).A lack of persistence limits the efficacy of adoptive-cell therapies (ACT), including chimeric antigen receptor T-cell therapies, for solid tumors. Three studies from Hu and colleagues, Conti and colleagues, and Chang and colleagues, report that the level of expression of the transcription factor BACH2 is important in determining the persistence and function of cells for ACT. High-level overexpression of BACH2 promotes quiescence, enabling persistence but limiting function, and thereby hinders tumor control. In contrast, low-level BACH2 expression, which the different groups achieve through distinct approaches, leads to persistence with potent antitumor function upon transfer in preclinical models. The data highlight the complexity of fine-tuning cells for ACT.Hu T, …, Wu T. Nat Immunol 2026 Jan 16;DOI:10.1038/s41590-025-02388-0.Conti AG, …, Roychoudhuri R. Nat Immunol 2026 Jan 16;DOI:10.1038/s41590-025-02389-z.Chang T-C, …, Singh N. Nat Immunol 2026 Jan 16;DOI:10.1038/s41590-025-02391-5.TAMs are neuroregenerative in tumors and spinal cord injury (From NIAID via Wikimedia Commons).Tumor-associated macrophages (TAMs) are immunosuppressive; yet how they impact intratumoral nerve infiltration, which can support tumor growth, has not been determined. Using both mouse models and human samples, Dolci and colleagues show that TAMs exhibit a neural growth signature and enhance neural growth in tumors. TAM-induced neural growth is driven by secreted phosphoprotein 1 (SPP1) and mTORC2 activation. In addition, adoptive transfer of TAMs in severe complete-compressive-contusive spinal cord injury results in improved neuronal growth and motor function recovery. The neuroregenerative potential of TAMs could therefore be harnessed for neural repair after injury or inhibited to prevent cancer growth.Dolci S, …, Decimo I. Immunity 2026 Jan 26;59;438–457.e16.Dead cell-associated neoantigens induce tumor immunogenicity (From Laboratoires Servier via Wikimedia Commons).How neoantigens from dead tumor cells induce immune responses has not been completely characterized. Lim and colleagues utilize adoptive transfer experiments, as well as whole-exome sequencing, to determine the antigenic visibility of tumors to CD8+ T cells in a chemical carcinogen tumor model. The authors use DNGR-1–deficient mice, which lack the conventional type 1 dendritic cells receptor for F-actin exposed on dead cells, and also tether model antigens to F-actin, which enhances DNGR-1–dependent cross-presentation, to show that these dead cell–associated neoantigens are immunogenic and induce CD8+ T-cell priming of cytoskeletal neoantigens. Therefore, considering dead cell–associated neoantigen cross presentation is important in cancer vaccine design.Lim KHJ, …, Reis e Sousa C. Nat Immunol 2026 Jan 02;27,72–81.