Oncoimmunology最新文献

{"title":"Bi-directional support of T lymphoma and a lymphoma-associated monocyte population involving Notch signaling in mice.","authors":"Sigrid Dubois, Yetzali Claudio-Medina, Jennifer L Marte, James L Gulley, Juergen R Mueller","doi":"10.1080/2162402X.2026.2713290","DOIUrl":"10.1080/2162402X.2026.2713290","url":null,"abstract":"<p><p>Tumor-induced manipulations of myelomonocytic differentiation have been widely reported. Here, we describe the elicitation of a tumor-supportive cell type in a T lymphoma model in mice. We observed that the development of T lymphoma coincided with the appearance of a lymphoma-associated monocytic cell type (LAM) of host origin accompanied by a diminished dendritic cell (DC) population. RNA-sequencing and cytometric analyses revealed that LAMs shared markers with both DCs and with resident macrophages, most closely resembling monocyte-derived DCs (moDCs). The numbers of T lymphoma cells were negatively affected by reducing LAMs suggesting a helper function of LAMs for tumor growth. LAMs expressed Notch ligands, and treatments of lymphoma-carrying mice with Notch signaling-inhibitors LY3039478 and DAPT selectively decreased expansions of T lymphomas with or without Notch1 mutations, respectively. Mature LAMs did not proliferate in the periphery. Instead, their expansion resulted from altered myelomonocytic differentiation in the bone marrows of lymphoma-carrying mice with increases in common monocyte/DC precursors but with reduced granulocyte, monocyte and DC precursor populations. These data suggest that developing T lymphomas are capable of reprogramming monocyte/DC differentiation to increase the numbers of a tumor-promoting DC type, attract it to tumor locations and may engage in Notch ligand-dependent signaling to support lymphoma survival.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"15 1","pages":"2713290"},"PeriodicalIF":6.2,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13449828/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148680578","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sialic acid <i>cis</i>-ligands as modulators of Siglec function in cancer immunity.","authors":"Anne H C Valk, Matthia G M Boros, Fabian Schuurmans, Gosse J Adema, Lenneke A M Cornelissen","doi":"10.1080/2162402X.2026.2752647","DOIUrl":"https://doi.org/10.1080/2162402X.2026.2752647","url":null,"abstract":"<p><p>The Siglec-sialoglycan axis is an emerging glyco-immune checkpoint in cancer. This is supported by the frequent upregulation of both Siglecs and sialoglycans in the tumor microenvironment. Siglecs are receptors expressed on immune cells that recognize sialoglycans, carbohydrate structures terminated by sialic acid. Most Siglec receptor family members are inhibitory and suppress immune cell activation through the recruitment of SHP-1 and SHP-2 phosphatases. It is well established that Siglecs expressed by immune cells bind ligands present on other cells, including tumor and stromal cells (<i>trans</i>-interactions). However, immune cells themselves also express sialoglycans that can serve as ligands for Siglecs on the same cell surface (<i>cis</i>-interactions). Over the past two decades, numerous studies have addressed how Siglec <i>trans</i>-engagement facilitates immunosuppression in the tumor microenvironment. The role of <i>cis</i>-interactions in regulating Siglec function and their impact on immune cell activity, however, remains an underexplored topic for most Siglec family members. This review discusses how <i>cis</i>-ligands modulate Siglec function, the mechanisms regulating sialic acid expression on immune cell surfaces, and the functional relevance of <i>cis</i>-interactions expressed by immune cells in the tumor microenvironment. A better understanding of these processes may facilitate the development of next-generation therapeutics targeting the Siglec-sialoglycan axis in cancer.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"15 1","pages":"2752647"},"PeriodicalIF":6.2,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149301450","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Real-world comparative outcomes of first-line immune combinations (ICI-ICI vs ICI-TKI) in metastatic renal cell carcinoma with sarcomatoid features.","authors":"Sara Elena Rebuzzi, Fabrizio Di Costanzo, Roberto Filippi, Pasquale Rescigno, Giuseppe Fornarini, Alessio Signori, Cristina Masini, Roberto Iacovelli, Martina Fanelli, Alberto Dalla Volta, Marilena Di Napoli, Giandomenico Roviello, Annalisa Guida, Cristian Lolli, Claudia Caserta, Rossana Berardi, Mariella Sorarù, Laura Lombardo, Francesco Pierantoni, Elena Verzoni, Alessia Mennitto, Sarah Scagliarini, Marcello Tucci, Maria Giuseppa Vitale, Carlo Messina, Lucia Bonomi, Luca Tondulli, Filippo Maria Deppieri, Francesca La Russa, Luigi Formisano, Cinzia Ortega, Brigida Anna Maiorano, Arianna Dri, Silvia Zai, Emilia Cocorocchio, Michele De Tursi, Emanuela Fantinel, Vincenza Conteduca, Cecilia Nasso, Camilla Sansi, Franco Nolè, Giulia Zago, Enrico Bronte, Giovanni Bozza, Francesca Bertolotti, Noemi Montobbio, Giuseppe Luigi Banna, Sebastiano Buti, Davide Bimbatti","doi":"10.1080/2162402X.2026.2751848","DOIUrl":"10.1080/2162402X.2026.2751848","url":null,"abstract":"<p><strong>Introduction: </strong>Although first-line immune-based combinations have reshaped the management of metastatic renal cell carcinoma (mRCC), relevant unmet clinical needs remain. Sarcomatoid feature is a negative prognostic factor that confers sensitivity to immunotherapy, yet the optimal ICI combination in this subgroup is still unclear.</p><p><strong>Methods: </strong>The Meet-URO 33 is an Italian multicenter retrospective/prospective observational study enrolling patients with mRCC receiving first-line systemic therapy in routine clinical practice. In the present sub-analysis, objective response and survival outcomes were compared between ICI-ICI and ICI-TKI regimens in patients with documented sarcomatoid differentiation and IMDC intermediate-/poor-risk disease.</p><p><strong>Results: </strong>Among 1695 patients enrolled from 58 centers, 180 (10.6%) had sRCC and among them, 107 (58.2%) were intermediate-risk and 56 (30.4%) were poor-risk. With a median follow-up of 21.8 months, in the I/P-sRCC population with available data (<i>n</i> = 155), univariable analysis showed longer overall survival (OS) with ICI-ICI compared to ICI-TKI (HR 0.58, <i>p</i> = 0.04). However, in propensity score-weighted analyses, point estimates slightly favored ICI-ICI, but no statistically significant differences were observed for OS, PFS, or ORR.</p><p><strong>Conclusions: </strong>In this real-world analysis comparing ICI-ICI and ICI-TKI in sarcomatoid mRCC, propensity score-weighted models showed no statistically significant differences between treatment combinations on clinical outcomes. These findings highlight the relevance of baseline disease and patients characteristics in shaping treatment outcomes and confirm the effectiveness of ICI-containing combinations in the treatment of sarcomatoid mRCC.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"15 1","pages":"2751848"},"PeriodicalIF":6.2,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13699842/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149246981","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transglutaminase 2 regulates innate immunity: mechanisms and therapeutic implications.","authors":"Manuela D'Eletto, Luca Occhigrossi, Fiorella Colasuonno, Veronica Bellanca, Federica Di Sano, Carla Montesano, Fabiola Ciccosanti, Yufang Shi, Mauro Piacentini, Federica Rossin","doi":"10.1080/2162402X.2026.2665505","DOIUrl":"10.1080/2162402X.2026.2665505","url":null,"abstract":"<p><p>Innate immunity constitutes the primary barrier against invading pathogens and plays a crucial role in coordinating the initiation and modulation of adaptive immune responses. Transglutaminase 2 (TG2), a ubiquitously expressed multifunctional enzyme, has recently been identified as a key regulator of innate immune signaling. Mounting evidence highlights TG2's involvement in modulating type I interferons and pro-inflammatory cytokines in response to microbial infections and cellular stress, serving as an critical element in diverse signaling pathways. TG2 engages in various immune-related processes, such as inflammation, phagocytosis, and host defense, by integrating into essential intracellular signaling cascades. In this review, we synthesize the current knowledge of TG2's roles in the innate immune system, emphasizing its interactions with TBK1 (TANK-binding kinase 1)-a central node in type I interferon signaling-and other innate immune mediators. We also examine the implications of TG2 dysregulation in immune-mediated diseases and evaluate its promise as a therapeutic target. Collectively, this review integrates recent progress and encourages further exploration of TG2's multifaceted contributions to innate immunity.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"15 1","pages":"2665505"},"PeriodicalIF":6.2,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13134424/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147786359","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"B cells and humoral immunity in melanoma: regulatory and autoimmune-like features and implications for immunotherapy.","authors":"Lucy Booth, Madeena Mahmood, Xinyi Chen, Joanna Jacków-Malinowska, Sophia Tsoka, Thomas J Tull, Sophia N Karagiannis","doi":"10.1080/2162402X.2026.2638620","DOIUrl":"10.1080/2162402X.2026.2638620","url":null,"abstract":"<p><p>B cells and the humoral immune response are increasingly recognized as critical modulators of melanoma progression and immunotherapy outcomes. While checkpoint inhibitor (CPI) therapy was developed to target T cell exhaustion mechanisms, emerging evidence highlights the complexity and clinical relevance of B cell biology in this highly immunogenic cancer. Dysregulated B cell subsets, including enriched circulating naïve and immunosuppressive populations, and skewing toward immune-inert antibody isotypes such as IgG4, correlate with diminished Fc-mediated effector functions and poor survival. Regulatory B cells (Bregs) contribute to immune tolerance by inducing regulatory T cells (Tregs) and shaping the suppressive tumor microenvironment (TME) via the secretion of immunosuppressive cytokines (TGFβ and IL-10). While intratumoral B cells exhibit clonal expansion, somatic hypermutation, and polyreactivity, the expression of antibodies with high frequencies of unproductive sequences may support an active yet aberrant autoimmune-like humoral response. Conversely, mature class-switched memory B cells and tumor-resident B cell populations, including those assembled in tertiary lymphoid structures (TLSs), are associated with improved CPI responses. Dynamic changes in circulating B cell phenotypes and autoantibody profiles during CPI treatment further link humoral immunity to therapeutic efficacy and immune-related adverse events (irAEs). Collectively, these findings underscore a dual role for B cells in melanoma, supporting antitumor immunity or promoting immune escape, and highlight opportunities to target Bregs, correct isotype imbalance, and leverage B cell signatures as biomarkers. Monitoring humoral responses before and during CPI therapy may inform patient stratification, predict toxicity, and guide interventions to optimize immunotherapy outcomes.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"15 1","pages":"2638620"},"PeriodicalIF":6.2,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12969741/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147370543","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multi-platform analysis of the tumor immune microenvironment associated with breast cancer subtypes.","authors":"Lilly Anne Torland, Jürgen Geisler, Youness Azimzade, Astri Frafjord, Hogne Røed Nilsen, Linn Buer, Jon Lømo, Øystein Garred, Andliena Tahiri, Marianne Lyngra, Inger Øynebråten, Alexandre Corthay, Kristine Sahlberg, Vessela Kristensen, Xavier Tekpli","doi":"10.1080/2162402X.2025.2610535","DOIUrl":"10.1080/2162402X.2025.2610535","url":null,"abstract":"<p><p>Breast cancer is genetically and histologically heterogenous, and is influenced by a variety of factors, including the tumor microenvironment (TME). The PAM50 subtypes; Luminal A, Luminal B, Normal-like, Basal-like and Her2-enriched, are associated with different tumor phenotypes and overall survival. The quantity and quality of immune cell infiltration in breast tumors play a key role in cancer development and progression and are associated with survival and treatment response. We used multiplex immunohistochemistry, single-cell RNA sequencing, and two deconvolution algorithms to explore the immune landscape across PAM50 subtypes. Immunostaining of CD3⁺ T cells, tryptase⁺ mast cells, CD20⁺ B cells, CD68⁺ CD163⁺ macrophages, and CD66b⁺ granulocytes revealed marked differences in tumor immune infiltrates according to breast cancer subtypes. Luminal tumors were relatively deprived of T cells and B cells, while exhibiting sparse to moderate amounts of macrophage infiltration. In contrast, Her2-enriched tumors exhibited a moderate immune presence, with sparse to moderate T cell infiltration and moderate infiltration of B cells and macrophages. At the other end of the spectrum, Basal-like tumors stood out for their strikingly rich immune environment and are heavily infiltrated by T cells, B cells, and macrophages. The results from the single-cell and deconvolution analyses confirmed subtype-specific immune microenvironments, which also allowed us to observe increased levels of natural killer (NK) and CD8⁺ T cells in Her2-enriched and Basal-like subtypes. In conclusion, our findings demonstrate significant differences in the immune tumor microenvironment between the established breast cancer molecular subtypes.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"15 1","pages":"2610535"},"PeriodicalIF":6.2,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12818823/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145967390","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Trial watch: antibody-drug conjugates in cancer therapy.","authors":"Flora Doffe, Xiaolian Deng, Zhe Shen, Enfu Xue, Kristine Schauer, Guido Kroemer, Oliver Kepp","doi":"10.1080/2162402X.2026.2667160","DOIUrl":"10.1080/2162402X.2026.2667160","url":null,"abstract":"<p><p>Antibody-drug conjugates (ADCs) combine the target specificity of monoclonal antibodies with the cytotoxic potency of small-molecule payloads. In recent years ADCs have emerged as a clinically validated component of modern precision oncology. To date, more than a dozen ADCs have received FDA approval for oncologic indications, with additional agents approved regionally and hundreds of ADC-based regimens in clinical development. Collectively, these therapies have demonstrated clinical benefit across hematologic malignancies and solid tumors, including significant overall survival improvements in advanced phase clinical trials. In this Trial Watch, we provide an overview on available ADCs from early preclinical development to current clinical applications. We also summarize design principles underpinning clinically successful ADCs, including epitope targeting, linker chemistry, payload toxicity and drug-to-antibody ratio, and discuss how these features can influence pharmacokinetics, intracellular trafficking, bystander effect and toxicity. Finally, we discuss results from advanced-stage clinical trials and approved agents to define future directions.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"15 1","pages":"2667160"},"PeriodicalIF":6.2,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13155009/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147822524","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Spatial transcriptomics unveils immune cellular ecosystems associated with patient survival in diffuse large B-cell lymphoma.","authors":"Alba Diaz-Herrero, Héctor Fernando Pelaez-Prestel, Lucile Massenet-Regad, Maëva Veyssiere, Julien Calvani, Caterina Cristinelli, Jacqueline Lehmann-Che, Véronique Meignin, Catherine Thieblemont, Véronique Blanc, Vassili Soumelis, Pierre Tonnerre","doi":"10.1080/2162402X.2026.2660418","DOIUrl":"10.1080/2162402X.2026.2660418","url":null,"abstract":"<p><p>Diffuse large B-cell Lymphoma (DLBCL) is the most prevalent subtype of non-Hodgkin's lymphoma for which current therapeutic strategies remain insufficient, in part owing to heterogeneity in tumor biology and the immune microenvironment. The diffuse nature of DLBCL represents a challenge to elucidate how malignant and immune cells are spatially organized within the tumor microenvironment (TME), and how this organization impacts immune function and clinical outcome. Here, we performed a pilot spatial transcriptomics analysis of primary DLBCL tissue sections to resolve spatial gene expression patterns and cell-cell interactions, with key cellular features validated at the protein level. We identified six recurrent, spatially organized cellular ecosystems (Cell-Eco) defined by distinct immune compositions, transcriptional programs, and neighborhood architectures. Notably, ecosystems with similar immune cell abundance exhibited divergent functional states and opposite clinical associations, demonstrating that spatial context and local interactions, rather than cell-type frequency alone, shape immune function within the DLBCL TME. Building on these spatial ecosystems, we derived Cell-Eco gene signatures that generated prognostic scores and robustly stratified patient survival in large, independent DLBCL cohorts comprising more than 1000 cases. Across ecosystems, tumor-associated macrophages have emerged as the dominant spatial partners of malignant B cells, highlighting their central role in structuring the immune microenvironment. Together, these findings establish a spatially informed framework for DLBCL immune organization and demonstrate the prognostic relevance of tumor cellular architecture.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"15 1","pages":"2660418"},"PeriodicalIF":6.2,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13102037/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147730270","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"IL-15 trans-presentation at the innate-adaptive interface: mechanisms and translation in cancer immunotherapy.","authors":"Corey Keith Goldman","doi":"10.1080/2162402X.2026.2736333","DOIUrl":"10.1080/2162402X.2026.2736333","url":null,"abstract":"<p><p>Durable antitumor immunity requires innate activation, antigen presentation, lymphocyte priming, trafficking, and effector function. In immunologically cold tumors, deficient dendritic-cell and natural killer (NK)-cell activation limits the transition from tumor-antigen recognition to CD8 T-cell immunity. Interleukin-15 (IL-15) is a member of the common gamma-chain cytokine family with a distinctive receptor-delivery system at this innate-adaptive interface. In native trans-presentation, IL-15 is stabilized by IL-15 receptor alpha (IL-15Rα) on an antigen-presenting cell and presented to CD122/CD132 on an apposed NK or memory CD8 T cell. This contact-dependent arrangement supports NK-cell homeostasis, memory CD8 T-cell maintenance, and spatially restricted signaling while avoiding the CD25-dependent regulatory T-cell preference of IL-2. IL-12, IL-15, and IL-18 can generate cytokine-induced memory-like NK cells with enhanced recall. These programs are constrained by intrinsic CISH feedback and by tumor-associated TGF-<i>β</i>, PD-L1, TIGIT, adenosine, and other suppressive pathways. Pharmacologic IL-15 receptor agonizts such as N-803 reproduce selected receptor-binding features of trans-presentation but do not reproduce its native source-cell, contact, or spatial restrictions. The durable activity of intravesical N-803 plus bacillus Calmette-Guérin in BCG-unresponsive non-muscle-invasive bladder cancer establishes clinical relevance in a localized combination setting, whereas systemic solid-tumor studies have shown pharmacodynamic lymphocyte expansion with more limited or variable clinical activity. This narrative review synthesizes IL-15 receptor biology, innate and adaptive effector programs, counter-regulation, and clinical translation. It presents the 'innate bootstrap' as a mechanistic hypothesis: appropriately timed IL-15-axis engagement may strengthen an impaired innate-to-adaptive handoff, with efficacy determined by route, tissue context, partner therapy, exposure schedule, and patient selection.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"15 1","pages":"2736333"},"PeriodicalIF":6.2,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13613925/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149026428","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mast cell phenotypic remodeling toward a PD-1-positive, Chymase-negative phenotype is associated with metastatic melanoma and poor survival.","authors":"Julián A Gajón, Laura C Bonifaz, Ezequiel Fuentes-Panana, Samira Muñoz-Cruz","doi":"10.1080/2162402X.2026.2752644","DOIUrl":"10.1080/2162402X.2026.2752644","url":null,"abstract":"<p><p>Mast cells (MCs) display phenotypic heterogeneity across tissues and disease contexts, yet their relevance in melanoma remains unclear. Here, we investigated MC phenotypic programs associated with melanoma progression using high-dimensional phenotyping of MCs co-cultured with melanoma spheroids, trajectory inference, and transcriptomic analyzes. Human melanoma tissues showed differences in MC phenotypic composition despite comparable abundance between outcome groups, with metastatic melanomas enriched for Tryptase⁺ Chymase^- MCs. Melanoma exposure induced MC phenotypic remodeling, characterized by loss of lineage- and effector-associated features and increased PD-1 expression, with more pronounced changes following metastatic melanoma co-culture. Trajectory analysis was consistent with a continuum toward a PD-1⁺ Chymase^- phenotype, which was detected in melanoma tissues and enriched within intratumoral regions of metastatic melanomas. Experimentally defined protein changes were used to derive two MC-associated transcriptomic signatures with opposing clinical associations, reflecting lineage- and effector-enriched versus melanoma-remodeled programs. The MC-LE signature was associated with favorable survival and interferon-responsive pathways, whereas the MC-MR signature was associated with poorer survival and tumor-associated pathways. These transcriptomic associations extended beyond melanoma across multiple TCGA cancer cohorts, and independent analysis of MCs from healthy skin, basal cell carcinoma, and melanoma showed corresponding differences in MC-LE-related features. Together, these findings support distinct mast cell phenotypic programs associated with melanoma progression and identify a PD-1⁺ Chymase^- MC phenotype enriched in metastatic disease and linked to transcriptomic features of poor survival.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"15 1","pages":"2752644"},"PeriodicalIF":6.2,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13699823/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149247038","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}