ArticleCancer discovery2025
Cytotoxic NK Cells Impede Response to Checkpoint Immunotherapy in Melanoma with an Immune-Excluded Phenotype.
Article in Cancer discovery, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed.
- Circulating immune cell profiling in advanced cervical and endometrial cancer patients treated with PD-1 blockade, radiotherapy, and immune modulation in the PRIMMO trial.Frontiers in immunology · 2026Trial
- Spatial ecotype in tumor immune exclusion: from spatial architecture to therapeutic strategies.Molecular cancer · 2026Review
- The tumoural landscape of lymphocytes and immune pathways in immunotherapy-treated melanoma patients.Genes and immunity · 2026Article
- Unconventional functions of natural killer cells in homeostasis and disease.Journal of immunology (Baltimore, Md. : 1950) · 2026Review
- Review
- Integrated Single-Cell Profiling Reveals Dichotomous NK Cell Populations Associated with Immunosuppression in Solid Tumors.Cancer immunology research · 2026Article
- CD155 links tumor immunotype to epithelial-directed precision therapy beyond checkpoint inhibition in cervical cancer.Journal for immunotherapy of cancer · 2026Article
- A longitudinal, multi-omic atlas reveals the emergence of a spatially organized immunosuppressive ecosystem in resistant melanoma.Cell reports. Medicine · 2026Article
- IFNγ-dependent metabolic reprogramming restrains an immature, pro-metastatic lymphatic state in melanoma.Cancer cell · 2026Article
- CX3CR1-mediated immune networks in sepsis: implications for precision therapy.Cell death discovery · 2026Review
- Characterization of Lymphocyte Subsets in Peripheral Blood of Patients with Colorectal Cancer.Journal of gastrointestinal cancer · 2026Article
- Article
- Review
- Reprogramming natural killer cells in the tumor microenvironment: Challenges and therapeutic opportunities.Cytokine & growth factor reviews · 2025Review
- Ubiquitin-conjugating enzyme E2S serves as a prognostic marker for skin cutaneous melanoma.Translational cancer research · 2025Article
- Therapeutic Use of Integrin Signaling in Melanoma Cells: Physical Link with the Extracellular Matrix (ECM).Cancers · 2025Review
- Tumor-associated NK Cells Regulate Distinct CD8+ T-cell Differentiation Program in Cancer and Contribute to Resistance against Immune Checkpoint Blockers.Cancer discovery · 2025Article
- Single-Cell Sequencing Redefines Immune Heterogeneity and Communication Networks in ARDS: Toward Precision Therapeutics.International journal of genomics · 2025Review
Corrections and comments
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Authors and funding
23 authors.
Funding
Abstract
Immune checkpoint blockade (ICB) has revolutionized cancer treatment. Unfortunately, the inability of lymphocytes to infiltrate the tumor nest, a phenomenon known as immune exclusion, drastically limits ICB responsiveness. Analyzing the immune landscape of matched pre- and early on-treatment biopsies of patients with melanoma undergoing ICB therapy, we observed a significant increase in cytotoxic NK cells in early on-treatment biopsies from nonresponders. Spatial multiomic analyses revealed that, although NK cells colocalized with CD8+ T cells within the tumor bed in responding lesions, they were excluded from the tumor parenchyma in nonresponding lesions. Strikingly, pharmacologic depletion of NK cells in a unique melanoma mouse model exhibiting an immune-excluded phenotype unleashed immune infiltration of the tumor core and tumor clearance upon ICB exposure. Mechanistically, we show that NK cells are actively recruited to immune-excluded areas upon ICB exposure via the chemokine receptor CX3CR1 to suppress tumor infiltration and antitumor function of CD8+ T cells. SIGNIFICANCE: Immune exclusion is responsible for intrinsic resistance to ICB in about half of nonresponder patients. Our unexpected observation that targeting NK cell biology unleashes the recruitment and antitumor activity of CD8+ T cells in tumors with an immune-excluded phenotype offers a potential therapeutic avenue for this large patient population. See related commentary by Galvez-Cancino et al., p. 1777 See related article by Song et al., p. 1835.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.