Editorial: New tumor immune checkpoints and their applications in tumor immunotherapy

More than a century ago, William Coley observed that bacterial products could trigger tumor regression, a finding that laid the foundation for cancer immunotherapy despite the era's limited immunological knowledge. Today, we continue to pursue the same fundamental goal: equipping the immune system to recognize and eradicate malignant cells. The advent of immune checkpoint inhibitors (ICIs) targeting PD-1/PD-L1 and CTLA-4 has profoundly reshaped the therapeutic landscape for numerous malignancies. Yet durable clinical benefit remains limited to a subset of patients, and both primary and acquired resistance pose enduring challenges. This has spurred an intensive search for novel immune checkpoints and robust predictive biomarkers to cancer patients receiving ICIs and find no significant changes in liver attenuation or liver enzyme levels, offering reassuring evidence that these agents may not exacerbate hepatic steatosis or subclinical liver injury-a finding particularly relevant for managing patients with pre-existing metabolic liver disease. These clinical vignettes and systematic reviews underscore the need for a multidimensional evaluation framework that incorporates baseline patient characteristics, dynamic biomarker monitoring, and vigilant assessment of immune-related adverse events.The articles collected in this Research Topic illustrate the breadth and depth of current investigation into novel tumor immune checkpoints and their applications.Looking ahead, several priorities warrant attention. The functional overlap and contextdependent expression of immune regulatory molecules call for systematic combinatorial strategies grounded in mechanistic understanding, potentially pairing novel checkpoint blockade with epigenetic modulators, metabolic inhibitors, or rational vaccine platforms. Translating emerging targets from preclinical validation to clinical deployment will require coordinated efforts, innovative trial designs, and the integration of integrative multi-omics approaches-from genomics and transcriptomics to single-cell analyses-to delineate the interplay among tumor metabolism, immune regulation, and therapeutic response. The continued incorporation of artificial intelligence into diagnostic and predictive pipelines is poised to accelerate progress across these domains. We extend our sincere appreciation to all the authors, reviewers, and the editorial team for their contributions, and hope this collection will serve as a catalyst for further investigation, interdisciplinary collaboration, and ultimately the advancement of effective, personalized immunotherapy for patients with cancer.