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Paul and colleagues report the development and characterization of an antibody–drug conjugate targeting TRBC2 for the treatment of T cell malignancies.

Suicidal donor T lymphocytes halt GvHD thereby favoring the graft-versus-tumor effect in allogeneic BMT patients.

As presented at the 2025 World Conference on Lung Cancer, in a multiarm phase 2 trial, perioperative immunotherapy was safe and feasible in patients with resectable diffuse pleural mesothelioma, with exploratory data suggesting that ctDNA kinetics could be informative of tumor regression and post-treatment survival.

In a prespecified interim analysis of the randomized, double-blind phase 3 COMPASSION-15 trial, patients with advanced HER2-negative gastric/GEJ cancer treated with the anti-PD-L1/CTLA-4 bispecific Ab cadonilimab plus chemotherapy showed significantly improved overall survival compared with patients treated with placebo plus chemotherapy as first-line treatment.

Although individual genes that distinguish tumor-reactive CD8+ T cells from bystander T cells in tumors have been described, a functionally meaningful integrative signature has not been established. Here authors show that mutation-associated neoantigen-specific CD8+ tumor-infiltrating lymphocytes can be recognized by MANAscore, an algorithm that uses weighted expression levels of CXCL13, ENTPD1 and IL7R in single-cell RNAseq datasets of lung cancer and melanoma patients as input.

Anti-TRBC1 antibody–drug conjugates may offer a more potent T cell cancer therapy by bypassing the fratricide that may be limiting the efficacy of anti-TRBC1 CAR T cells in the clinical trial for patients with T cell cancers.

In a phase Ib trial, neoadjuvant nivolumab or nivolumab/relatlimab prior to chemoradiotherapy were well tolerated and liquid biopsy analyses show that undetectable ctDNA was associated with longer survival.

The advent of high-throughput T-cell receptor sequencing has allowed for the rapid and thorough characterization of the adaptive immune response. Here the authors show how deep learning can reveal both descriptive and predictive sequence concepts within the immune repertoire.

Adoptive T cell transfer studies in mice and in cancer patients have shown substantial potential, but also major barriers, for successful therapeutic outcomes. A new strategy may overcome some of these barriers. T cells can now be engineered with 'autocostimulation' properties along with chimeric receptors specific for tumor antigens (pages 1440–1449).

Anagnostou et al. present an improved predictor of response to immune checkpoint blockade that integrates estimates of tumor mutational burden corrected for tumor purity, RTK genomic alterations, a smoking-related mutational signature and HLA status.

Mutation associated neoantigens are a family of highly specific therapeutic targets for the treatment of cancer. Here, the authors describe the cryo-EM structure of an antibody bound to a neoantigen complex providing insights into the specificity of the antibody.

In a single-arm phase 2 study, enoblituzumab (a humanized, Fc-engineered, B7-H3-targeting antibody) was found to be safe and showed preliminary evidence of potential clinical activity in men with high-risk localized prostate cancer.

Genomic analyses in large cohorts of patients with cancer identify a new measure of tumor mutational burden, based on genomic regions that are unlikely to undergo loss, that is associated with therapeutic response to immunotherapy.

In a phase 2 trial, the combination of chemotherapy with durvalumab, an anti-PD-L1 antibody, exhibited promising clinical activity in patients with previously untreated, unresectable mesothelioma, with additional analyses providing insights into genomic and immunologic features potentially associated with response.

Chimeric antigen receptor T cells in the clinic currently target cell-type-specific extracellular antigens on malignant cells. Here, authors engineer tumor-specific chimeric antigen receptor T cells that target human leukocyte antigen-presented neoantigens derived from mutant intracellular proteins.

Single-cell RNA sequencing and T cell receptor sequencing are combined to identify transcriptional programs specific to mutation-associated neoantigen-specific T cells in non-small cell lung cancers treated with anti-PD-1, providing insights into resistance to PD-1 blockade.

In mouse models of pulmonary metastasis, adjuvant epigenetic therapy targeting myeloid-derived suppressor cells disrupts the premetastatic microenvironment after resection of primary tumours and inhibits the dissemination of residual tumour cells.

Enterotoxigenic Bacteroides fragilis, a bacterium from the intestinal flora, may promote colon tumor formation through a pathway that involves Stat3 expression and T helper type 17 immune responses.

Vaccination with BCG has been shown to induce a pre-priming effect in innate immune cells termed trained immunity. Here the authors re-engineer the BCG vaccine and show augmented immune responses, enhanced induction of trained immunity and improved antitumor efficacy in pre-clinical models of bladder cancer.

Tumors generate microenvironments that actively suppress the body's anti-tumor immune response. Kortylewski et al. restore immunity by delivering an siRNA against Stat3, a regulator of immune suppression, to myeloid and B cells using a CpG oligonucleotide that targets toll-like receptor 9.

Metabolic changes induced by hypoxia and extracellular ATP, acting through the transcription factors HIF1-α and AHR, regulate the differentiation of type 1 regulatory (T_reg1) cells.

High-throughput tissue arrays allow for evaluation of in vitro cellular responses and correlation to matrix composition.

Immune checkpoints refer to the plethora of inhibitory pathways that are crucial to maintaining self-tolerance. Tumour cells induce immune checkpoints to evade immunosurveillance. This Review discusses the progress in targeting immune checkpoints, the considerations for combinatorial therapy and the potential for additional immune-checkpoint targets.

The immune system's response to new tumours is complicated but seems to depend on where and when tumours develop. This will have to be much better understood to enlist a patient's immune defences in fighting cancer.

Stimulating engineered T cells with a powerful immunogen enhances their ability to kill tumor cells.

Signal transducer and activator of transcription (STAT) proteins help determine whether immune responses promote or inhibit tumours. Specifically, STAT3 increases tumour cell proliferation, survival and invasion and activates tumour-promoting inflammation, but also suppresses anti-tumour immune responses. STAT3 is therefore a promising target for cancer therapy.

Monoclonal antibodies (mAbs) that regulate the immune response are now being clinically evaluated as anticancer agents. This Review discusses their progress to date and the possibilities for combining these antibodies with other cancer treatments.

Successful translation of modern molecular immunology into effective cancer immunotherapy is threatened by regulatory barriers and challenges to the development of novel agents and combinatorial strategies through effective public-private partnerships. For its promise to be fully realized, both the National Cancer Institute and Food and Drug Administration must take active steps to help academic investigators and companies jointly navigate the pathways from laboratory to clinic.

Studies in metastatic melanoma, non-small-cell lung carcinoma and renal cell carcinoma indicate certain bacteria within the gut microbiota enhance clinical responses to checkpoint blockade.