Oncoimmunology最新文献

{"title":"The pancreatic tumor microenvironment of treatment-naïve patients causes a functional shift in γδ T cells, impairing their anti-tumoral defense.","authors":"Elena Lo Presti, Francesca Cupaioli, Daniela Scimeca, Elettra Unti, Vincenzo Di Martino, Rossella Daidone, Michele Amata, Nunzia Scibetta, Erinn Soucie, Serena Meraviglia, Juan Iovanna, Nelson Dusetti, Andrea De Gaetano, Ivan Merelli, Roberto Di Mitri","doi":"10.1080/2162402X.2025.2466301","DOIUrl":"10.1080/2162402X.2025.2466301","url":null,"abstract":"<p><p>Pancreatic ductal adenocarcinoma (PDAC) presents a unique challenge for researchers due to its late diagnosis caused by vague symptoms and lack of early detection markers. Additionally, PDAC is characterized by an immunosuppressive microenvironment (TME), making it a difficult tumor to treat. While γδ T cells have shown potential for anti-tumor activity, conflicting studies exist regarding their effectiveness in pancreatic cancer. This study aims to explore the hypothesis that the PDAC TME hinders the anti-tumor capabilities of γδ T cells through blockade of cytotoxic functions. For this reason, we chose to enroll PDAC treatment-naive patients to avoid the possibility of therapy modifying the TME. By flow cytometry, our research findings indicate that the presence of γδ T cells among CD45+ cells in tumor tissue is lower compared to CD66+ cells, but higher than in blood. Circulating Vδ1 T cells exhibit a terminal effector memory phenotype (TEMRA) more than Vδ2 T cells. Interestingly, Vδ1 and Vδ2 T cells appear to be more prevalent at different stages of tumor development. In our <i>in vitro</i> culture using conditioned medium derived from Patient-derived organoids ;(PDOs), we observed a shift in expression markers in γδ T cells of healthy individuals toward an activation and exhaustion phenotype, as confirmed by scRNA-seq analysis extracted from a public database. A deeper understanding of γδ T cells in PDAC could be valuable for developing novel therapies aimed at mitigating the impact of the pancreatic tumor microenvironment on this cell population.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"14 1","pages":"2466301"},"PeriodicalIF":6.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11834455/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143411294","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 transpresentation by ovarian cancer cells improves CD34⁺ progenitor-derived NK cell's anti-tumor functionality.","authors":"M Vidal-Manrique, T Nieuwenstein, L Hooijmaijers, P K J D de Jonge, M Djojoatmo, J Jansen, A B van der Waart, R Brock, H Dolstra","doi":"10.1080/2162402X.2025.2465010","DOIUrl":"10.1080/2162402X.2025.2465010","url":null,"abstract":"<p><p>Ovarian cancer (OC) is the most lethal gynecological malignancy. As high numbers of Natural Killer (NK) cells in ascites associate with improved survival, the adoptive transfer of allogeneic NK cells is an attractive therapeutic strategy. An approach to further improve NK cell expansion and anti-tumor functionality post-infusion includes IL-15 transpresentation (transIL-15), which involves surface expression of the IL-15 cytokine bound to IL-15Rα. However, others have substantiated that systemic administration of ALT/N-803, a soluble molecule mimicking transIL-15, leads to T cell-mediated rejection of the infused allogeneic NK cell product. In addition, whether transIL-15 induce superior expansion and functionality of our hematopoietic progenitor cell-derived NK cells (HPC-NK) remains understudied. Here, we propose to transfect OC cells with IL-15 and IL-15Rα mRNA and evaluate HPC-NK cell stimulation <i>in vitro</i>. Co-transfection of both mRNAs resulted in surface co-expression of both components, thus mimicking the transIL-15. Importantly, co-culture of HPC-NK cells with transIL-15 OC cells resulted in superior proliferation, IFNγ production, cytotoxicity and granzyme B secretion. Furthermore, we observed uptake of IL-15Rα by HPC-NK cells when co-cultured with transIL-15 OC cells, which associates with NK cell long-term proliferation and survival. Superior killing and granzyme B secretion were also observed in transIL-15 OC spheroids. Our results demonstrate that local delivery of IL-15 and IL-15Rα mRNA to OC tumors may be a safer strategy to boost HPC-NK cell therapy of OC through IL-15 transpresentation.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"14 1","pages":"2465010"},"PeriodicalIF":6.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11834524/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143442423","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":"Paradoxical control of multifocal mammary oncogenesis by radiation therapy.","authors":"Lorenzo Galluzzi, Aitziber Buqué","doi":"10.1080/2162402X.2025.2458886","DOIUrl":"10.1080/2162402X.2025.2458886","url":null,"abstract":"<p><p>In an immunocompetent mouse model of multifocal, metachronous HR⁺ mammary carcinogenesis, we have recently demonstrated that a superior control of primary neoplastic lesions by focal radiotherapy does not necessarily translate into improved oncosuppression at non-irradiated (pre)malignant tissues. These data point to a link between local tumor control by radiotherapy and systemic oncogenesis that remains to be fully understood.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"14 1","pages":"2458886"},"PeriodicalIF":6.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11776481/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143053977","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":"Differential distribution of immune checkpoints across molecular subtypes of colorectal cancer.","authors":"Sofia Edin, Björn Gylling, Xingru Li, Åsa Stenberg, Anna Löfgren-Burström, Bethany van Guelpen, Agnes Ling, Ingrid Ljuslinder, Richard Palmqvist","doi":"10.1080/2162402X.2025.2546406","DOIUrl":"https://doi.org/10.1080/2162402X.2025.2546406","url":null,"abstract":"<p><p>The recent introduction of immune checkpoint inhibitor therapy has significantly improved outcomes for patients with colorectal cancer (CRC). The most pronounced clinical benefits were observed in patients with immunogenic microsatellite instable (MSI)/deficient MMR (dMMR) tumors. However, emerging evidence indicates that a subset of patients with microsatellite stable tumors may also respond to therapy. Finding predictive markers to identify these patients is critical. In this study, we analyzed the immunohistochemical expression of immune checkpoints CTLA-4, PD-1, and PD-L1 using multispectral imaging in 151 CRC patients with defined molecular characteristics. Consistent with prior reports, MSI tumors had higher levels of all immune checkpoints analyzed than microsatellite stable tumors. Notably, distinct patterns of immune checkpoint expression were associated with <i>KRAS</i> and <i>BRAF</i> mutation status. <i>KRAS-</i>mutated tumors showed lower, and <i>BRAF-</i>mutated tumors higher, expression of immune checkpoints compared to wild-type/wild-type tumors. The strongest association with <i>KRAS</i> and <i>BRAF</i> mutations was observed for PD-L1 expression. The relationship between PD-L1 and <i>KRAS/BRAF</i>-mutational status was validated in a second cohort of 527 CRC patients, finding the association for PD-L1 expression in both stroma and in tumor cells. Furthermore, the role of <i>BRAF</i> mutation on immunity in CRC was found to be partly independent of MSI status. The strongest prognostic role was found for PD-L1 in stroma, underscoring the clinical significance of this marker. In conclusion, our findings suggest that <i>KRAS</i> and <i>BRAF</i> mutations, alongside MSI, may serve as valuable biomarkers for identifying CRC patient subgroups likely to benefit from immune checkpoint blockade in CRC.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"14 1","pages":"2546406"},"PeriodicalIF":6.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12372490/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144975165","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":"A dual compartment peripheral blood signature of soluble and membrane-bound immune checkpoints predicts outcome in lymphoma patients.","authors":"Joao Gorgulho, Timo Trenkner, Eva Kinkel, Britta Fritzsche, Paul Kachel, Sven Peine, Urte Matschl, Markus Altfeld, Samuel Huber, Ansgar W Lohse, Winfried Alsdorf, Carsten Bokemeyer, Angelique Hoelzemer, Wilfredo Garcia Beltran, Johann von Felden","doi":"10.1080/2162402X.2025.2543511","DOIUrl":"https://doi.org/10.1080/2162402X.2025.2543511","url":null,"abstract":"<p><p>Lymphomas, particularly aggressive non-Hodgkin lymphomas (NHL), remain challenging due to poor outcomes in a subset of patients who fail initial therapy. Current minimally invasive biomarkers for risk stratification need further improvement. Immune checkpoint inhibitors (ICIs), while with limited efficacy in NHL, highlight the immune system's crucial role in cancer control. This study investigated the predictive and prognostic potential of soluble immune checkpoints (sICs) and their membrane-bound isoforms in the peripheral blood of lymphoma patients. Levels of sCD27, sCD28, and sCD80 were measured using multiplex immunoassay in 100 lymphoma patients and 62 healthy donors (HD). Expression of membrane-bound isoforms on PBMCs was analyzed via flow cytometry in 40 patients and 10 HD. All three sICs were significantly higher in lymphoma patients compared to HD. High levels were associated with significantly impaired disease control (DC) and survival at 12 and 24 months, progression free-survival (PFS) and overall survival (OS). The highest prediction capacity was achieved when assessing all three molecules in a combined score (p_PFS < 0.001, p_OS = 0.013, for score 0 vs 3: DC_12mo:85% vs 18.5%, OS_24mo:87% vs 27%). Integrating expression of related membrane-bound markers on PBMCs led to a highly robust peripheral blood-based biomarker score comprising the soluble and membrane-bound compartments (2COMPIC-Score:3 sICs + 7 PBMC subsets) (p_PFS < 0.001, HR_PFS = 18.1;p_OS = 0.001,HR_OS = 19.2), corroborated by multivariate analysis, outperforming the clinically validated NCCN-IPI prognostic score. We unveil the potential of combining different minimally invasive liquid biopsy-based immune checkpoint assessments into a robust clinical score for prognostic prediction in lymphoma, mainly B(cell)-NHL. Pending prospective validation, our findings could aid clinicians in guiding therapeutic decisions.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"14 1","pages":"2543511"},"PeriodicalIF":6.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12396130/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144975170","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":"Benzodiazepines interfere with the efficacy of pembrolizumab-based cancer immunotherapy. Results of a nationwide cohort study including over 50,000 participants with advanced lung cancer.","authors":"Léa Montégut, Adrien Rousseau, Cinzia Ungolo, Lisa Derosa, Marine Fidelle, Carolina Alves Costa Silva, Bertrand Routy, Laurence Zitvogel, Benjamin Besse, Edoardo Pasolli, Guido Kroemer","doi":"10.1080/2162402X.2025.2528955","DOIUrl":"10.1080/2162402X.2025.2528955","url":null,"abstract":"<p><p>We previously reported that elevated levels of diazepam binding inhibitor (DBI), also called 'endozepine' because it acts as an endogenous benzodiazepine equivalent on the gamma-aminobutyric acid type A receptor, constitutes a potential risk factor for the diagnosis of non-small cell lung cancer (NSCLC). Antibody-mediated neutralization of DBI improved the immunosurveillance of NSCLC in preclinical models with and without immunotherapy targeting programmed cell death protein 1 (PD-1). A pilot study in a small French-Canadian cohort (<i>n</i> = 205) suggested that benzodiazepine (BZD) use correlates with reduced progression-free survival in NSCLC patients receiving PD-1/PD-L1 blockade. Here, we report a retrospective analysis of the nation-wide French registry of advanced NSCLC patients treated with pembrolizumab. Among the eligible NSCLC patients surviving ≥2 months after treatment initiation (<i>n</i> = 31,479), 37.7% (<i>n</i> = 11,878) received at least two prescriptions of benzodiazepines within 90 days before to 30 days after treatment initiation. Compared to non-users (<i>n</i> = 19,601), BZD users had significantly reduced overall survival (hazard ratio = 1.08, 95% CI: 1.04-1.12, <i>p</i> < 0.001), an effect that persisted after correction using inverse probability of treatment weighting (IPTW) on sociodemographic, clinical, oncologic, and comedication variables. In a subset of 556 patients from the ONCOBIOTICS study, benzodiazepine use was associated with signs of intestinal dysbiosis and alterations in the TOPOSCORE, a prognostic marker linked to poorer outcomes in cancer patients receiving immunotherapy. We conclude that benzodiazepine use may be an independent negative prognostic factor for NSCLC patients under pembrolizumab-based immunotherapy. Future studies must determine whether withdrawal of benzodiazepines or neutralization of DBI improves the clinical response to immunotherapy.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"14 1","pages":"2528955"},"PeriodicalIF":6.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12233713/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144561562","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":"The human STING agonist E7766 induces immunogenic tumor clearance, independent of tumor-intrinsic STING expression in the <i>KRAS^G12D/+ Trp53^-/-</i> murine model of sarcoma.","authors":"Karys M Hildebrand, Kurt N Hildebrand, Carolina Salazar Arcila, Kayla Marritt, Jahanara Rajwani, Golpira Elmi Assadzadeh, Antoine Dufour, Frank R Jirik, Michael J Monument","doi":"10.1080/2162402X.2025.2534912","DOIUrl":"10.1080/2162402X.2025.2534912","url":null,"abstract":"<p><p>Soft tissue sarcomas (STS) are aggressive high-fatality cancers that affect children and adults. Most STS subtypes harbor an immunosuppressive tumor microenvironment (TME) and respond poorly to immunotherapy. Therapies capable of dismantling the immunosuppressive TME are needed to improve sensitivity to emerging immunotherapies. Activation of the Stimulator of INterferon Genes (STING) pathway has shown promising anti-tumor effects in preclinical models of carcinoma, but evaluations in sarcoma are lacking. Herein, we sought to examine the immune modulation and therapeutic efficacy of three translational small molecule STING agonists in an immunologically cold model of STS. Three classes of STING agonists, ML RR-S2 CDA, MSA-2, and E7766 were evaluated in an orthotopic KrasG12D/+ Trp53-/- model of STS. Dose titration survival studies, cytokine serology, and tumor immune phenotyping were used to examine STING agonist efficacy following intra-tumoral treatment. All STING agonists significantly increased survival time, however, only E7766 resulted in durable tumor clearance, inducing CD8+ T-cell infiltration and activated lymphocyte transcriptomic signatures in the TME. Antibody depletion was used to assess the dependency of treatment responses on CD8+ T-cells, showing that in their absence, tumor clearance did not occur following E7766 therapy. Using STING deficient mice, and CRISPR/Cas9 gene editing, we demonstrated that STS clearance following STING therapy was dependent on host STING and not tumor-intrinsic STING pathway functionality. E7766 represents a promising candidate able to remodel the TME of murine STS tumors toward an inflamed phenotype independent of tumor-intrinsic STING functionality, and should be considered for potential translation in STS treatment.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"14 1","pages":"2534912"},"PeriodicalIF":6.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12296111/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144683485","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":"Correction.","authors":"","doi":"10.1080/2162402X.2025.2538308","DOIUrl":"10.1080/2162402X.2025.2538308","url":null,"abstract":"","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"14 1","pages":"2538308"},"PeriodicalIF":6.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12309527/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144715162","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":"A versatile silica nanoparticle platform for induction of T cell responses - applied for therapeutic vaccination against HPV16 E6/E7-positive tumors in MHC-humanized mice.","authors":"Sebastian Kruse, Lia T Fricke, Samantha Zottnick, Ann-Katrin Schlosser, Agnieszka K Grabowska, Eva Feidt, Philipp Uhl, Ellen Junglas, Jonas D Förster, Josephine Blersch, Philip Denner, Manina Günter, Stella E Autenrieth, Eugenio Fava, Walter Mier, Armin Kübelbeck, Angelika B Riemer","doi":"10.1080/2162402X.2025.2548002","DOIUrl":"10.1080/2162402X.2025.2548002","url":null,"abstract":"<p><p>Therapeutic vaccines represent a promising treatment option for (pre)cancerous lesions, such as human papillomavirus-induced malignancies. They act via administration of tumor-specific antigens, leading to induction of antigen-specific cytotoxic T cell responses. However, vaccination efficiency is often limited when the antigen is administered alone, due to antigen instability and inefficient uptake by antigen-presenting cells (APCs). To address these limitations, nanoparticle-based vaccine delivery systems are currently under investigation. Here, we present a novel silica nanoparticle (SiNP)-based vaccine delivery platform that can be applied for the treatment of various diseases and cancer types. We show that surface-functionalized SiNPs are non-cytotoxic and quickly taken up by APCs. Incorporation of a linker/solubilizer sequence N-terminal of the epitope allows attachment of peptides regardless of their solubility as well as efficient processing and surface presentation by APCs. Whole-body distribution studies confirmed retention of the antigen at the injection site and decelerated excretion when connected to SiNPs. Furthermore, treatment with SiNPs, especially when combined with the adjuvant poly(I:C), resulted in activation of dendritic cells capable of priming CD8⁺ T cells. In C57BL/6 and MHC-humanized A2.DR1 mice, the SiNP-based vaccinations induced epitope-specific CD8⁺ T cells. Moreover, they exhibited anti-tumor activity and provided a survival benefit in a tumor model using HPV16 E6/E7-expressing PAP-A2 cells. Thus, the novel SiNP platform represents a promising new vehicle for therapeutic vaccine delivery.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"14 1","pages":"2548002"},"PeriodicalIF":6.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12382477/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145114577","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":"Clinical impact of cancer cachexia on the outcome of patients with non-small cell lung cancer with PD-L1 tumor proportion scores of ≥50% receiving pembrolizumab monotherapy versus immune checkpoint inhibitor with chemotherapy.","authors":"Hayato Kawachi, Tadaaki Yamada, Motohiro Tamiya, Yoshiki Negi, Takashi Kijima, Yasuhiro Goto, Akira Nakao, Shinsuke Shiotsu, Keiko Tanimura, Takayuki Takeda, Asuka Okada, Taishi Harada, Koji Date, Yusuke Chihara, Isao Hasegawa, Nobuyo Tamiya, Yuki Katayama, Naoya Nishioka, Kenji Morimoto, Masahiro Iwasaku, Shinsaku Tokuda, Takayuki Shimose, Koichi Takayama","doi":"10.1080/2162402X.2024.2442116","DOIUrl":"10.1080/2162402X.2024.2442116","url":null,"abstract":"<p><p>This retrospective, multicenter cohort study aimed to determine whether cancer cachexia serves as a biomarker for determining the most effective treatment for patients having non-small-cell lung cancer (NSCLC) with high programmed death ligand 1 (PD-L1) expression treated with immune checkpoint inhibitors (ICIs) alone or combined with chemotherapy (ICI/chemotherapy). We included 411 patients with advanced NSCLC with a PD-L1 tumor proportion score of ≥50%. The patients were treated with pembrolizumab monotherapy or ICI/chemotherapy. Cancer cachexia was defined as a weight loss of >5% of the total body weight or a body mass index of <20 kg/m² coupled with an additional weight loss of >2% within 6 months before starting treatment. Eighty-five (21%) patients met the cancer cachexia criteria. Overall survival (OS) was significantly shorter in patients with cachexia than in those without cachexia in both the pembrolizumab monotherapy group (17.2 vs. 35.8 months, <i>p</i> < 0.001) and the ICI/chemotherapy group (27.0 months vs. not reached, <i>p</i> = 0.044). However, after stratifying by cancer cachexia status, no significant difference in OS was observed between the pembrolizumab monotherapy and chemoimmunotherapy groups, regardless of cachexia. In conclusion, ICI/chemotherapy offers limited benefits for NSCLC patients with high PD-L1 expression and concurrent cancer cachexia. Considering the frailty associated with cachexia, ICI monotherapy may be preferred to ICI/chemotherapy for these patients. New interventions that can better address the negative prognostic impact of cachexia in patients treated using ICIs with or without chemotherapy remain warranted.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"14 1","pages":"2442116"},"PeriodicalIF":6.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11651275/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142839944","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}