Oncoimmunology最新文献

{"title":"SIGLEC15, negatively correlated with PD-L1 in HCC, could induce CD8+ T cell apoptosis to promote immune evasion.","authors":"Zheng Chen, Mincheng Yu, Bo Zhang, Lei Jin, Qiang Yu, Shuang Liu, Binghai Zhou, Jiuliang Yan, Wentao Zhang, Xiaoqiang Li, Yongfeng Xu, Yongsheng Xiao, Jian Zhou, Jia Fan, Mien-Chie Hung, Qinghai Ye, Hui Li, Lei Guo","doi":"10.1080/2162402X.2024.2376264","DOIUrl":"10.1080/2162402X.2024.2376264","url":null,"abstract":"<p><p>Functional roles of SIGLEC15 in hepatocellular carcinoma (HCC) were not clear, which was recently found to be an immune inhibitor with similar structure of inhibitory B7 family members. SIGLEC15 expression in HCC was explored in public databases and further examined by PCR analysis. SIGLEC15 and PD-L1 expression patterns were examined in HCC samples through immunohistochemistry. SIGLEC15 expression was knocked-down or over-expressed in HCC cell lines, and CCK8 tests were used to examine cell proliferative ability in vitro. Influences of SIGLEC15 expression on tumor growth were examined in immune deficient and immunocompetent mice respectively. Co-culture system of HCC cell lines and Jurkat cells, flow cytometry analysis of tumor infiltrated immune cells and further sequencing analyses were performed to investigate how SIGLEC15 could affect T cells in vitro and in vivo. We found SIGLEC15 was increased in HCC tumor tissues and was negatively correlated with PD-L1 in HCC samples. In vitro and in vivo models demonstrated inhibition of SIGLEC15 did not directly influence tumor proliferation. However, SIGLEC15 could promoted HCC immune evasion in immune competent mouse models. Knock-out of <i>Siglec15</i> could inhibit tumor growth and reinvigorate CD8+ T cell cytotoxicity. Anti-SIGLEC15 treatment could effectively inhibit tumor growth in mouse models with or without mononuclear phagocyte deletion. Bulk and single-cell RNA sequencing data of treated mouse tumors demonstrated SIGLEC15 could interfere CD8+ T cell viability and induce cell apoptosis. In all, SIGLEC15 was negatively correlated with PD-L1 in HCC and mainly promote HCC immune evasion through inhibition of CD8+ T cell viability and cytotoxicity.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"13 1","pages":"2376264"},"PeriodicalIF":6.5,"publicationDate":"2024-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11236293/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141581265","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":"Short-term cultured tumor fragments to study immunotherapy combinations based on CD137 (4-1BB) agonism.","authors":"Iñaki Eguren-Santamaría, Inmaculada Rodríguez, Claudia Herrero-Martin, Eva Fernández de Piérola, Arantza Azpilikueta, Sandra Sánchez-Gregorio, Elixabet Bolaños, Gabriel Gomis, Paula Molero-Glez, Enrique Chacón, José Ángel Mínguez, Santiago Chiva, Fernando Diez-Caballero, Carlos de Andrea, Álvaro Teijeira, Miguel F Sanmamed, Ignacio Melero","doi":"10.1080/2162402X.2024.2373519","DOIUrl":"10.1080/2162402X.2024.2373519","url":null,"abstract":"<p><p>Biomarkers for cancer immunotherapy are an unmet medical need. The group of Daniela Thommen at the NKI recently reported on novel methodologies based on short-term cultures of patient-derived tumor fragments whose cytokine concentrations in the supernatants and activation markers on infiltrating T cells were associated with clinical response to PD-1 blockade. We set up a similar culture technology with tumor-derived fragments using mouse tumors transplanted into syngeneic immunocompetent mice to test an agonist anti-CD137 mAb and its combinations with anti-PD-1 and/or anti-TGF-β. Increases in IFNγ concentrations in the tissue culture supernatants were detected upon in-culture activation with the anti-CD137 and anti-PD-1 mAb combinations or concanavalin A as a positive control. No other cytokine from a wide array was informative of stimulation with these mAbs. Interestingly, increases in Ki67 and other activation markers were substantiated in lymphocytes from cell suspensions gathered at the end of 72 h cultures. In mice bearing bilateral tumors in which one was excised prior to <i>in vivo</i> anti-CD137 + anti-PD-1 treatment to perform the fragment culture evaluation, no association was found between IFNγ production from the fragments and the <i>in vivo</i> therapeutic outcome in the non-resected contralateral tumors. The experimental system permitted freezing and thawing of the fragments with similar functional outcomes. Using a series of patient-derived tumor fragments from excised solid malignancies, we showed IFNγ production in a fraction of the studied cases, that was conserved in frozen/thawed fragments. The small tumor fragment culture technique seems suitable to preclinically explore immunotherapy combinations.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"13 1","pages":"2373519"},"PeriodicalIF":6.5,"publicationDate":"2024-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11236292/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141581264","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 impact of genetic deletion of TIGIT or PD-1 on melanoma-specific T-lymphocytes.","authors":"Gwenann Cadiou, Tiffany Beauvais, Lucine Marotte, Sylvia Lambot, Cécile Deleine, Caroline Vignes, Malika Gantier, Melanie Hussong, Samuel Rulli, Anne Jarry, Sylvain Simon, Bernard Malissen, Nathalie Labarriere","doi":"10.1080/2162402X.2024.2376782","DOIUrl":"10.1080/2162402X.2024.2376782","url":null,"abstract":"<p><p>Immune checkpoint (IC) blockade and adoptive transfer of tumor-specific T-cells (ACT) are two major strategies to treat metastatic melanoma. Their combination can potentiate T-cell activation in the suppressive tumor microenvironment, but the autoimmune adverse effects associated with systemic injection of IC blockers persist with this strategy. ACT of tumor-reactive T-cells defective for IC expression would overcome this issue. For this purpose, PD-1 and TIGIT appear to be relevant candidates, because their co-expression on highly tumor-reactive lymphocytes limits their therapeutic efficacy within the tumor microenvironme,nt. Our study compares the consequences of <i>PDCD1</i> or <i>TIGIT</i> genetic deletion on anti-tumor properties and T-cell fitness of melanoma-specific T lymphocytes. Transcriptomic analyses revealed down-regulation of cell cycle-related genes in PD-1^KO T-cells, consistent with biological observations, whereas proliferative pathways were preserved in TIGIT^KO T-cells. Functional analyses showed that PD-1^KO and TIGIT^KO T-cells displayed superior antitumor reactivity than their wild-type counterpart <i>in vitro</i> and in a preclinical melanoma model using immunodeficient mice. Interestingly, it appears that TIGIT^KO T-cells were more effective at inhibiting tumor cell proliferation <i>in vivo</i>, and persist longer within tumors than PD-1^KO T-cells, consistent with the absence of impact of TIGIT deletion on T-cell fitness. Taken together, these results suggest that TIGIT deletion, over PD-1 deletion, in melanoma-specific T-cells is a compelling option for future immunotherapeutic strategies.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"13 1","pages":"2376782"},"PeriodicalIF":6.5,"publicationDate":"2024-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11232637/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141564870","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":"Characterization of double-negative T cells in colorectal cancers and their corresponding lymph nodes.","authors":"Kazumi Okamura, Lifang Wang, Satoshi Nagayama, Makiko Yamashita, Tomohiro Tate, Saki Matsumoto, Manabu Takamatsu, Shigehisa Kitano, Kazuma Kiyotani, Yusuke Nakamura","doi":"10.1080/2162402X.2024.2373530","DOIUrl":"10.1080/2162402X.2024.2373530","url":null,"abstract":"<p><p>TCRαβ+ CD4- CD8- double-negative T (DNT) cells are minor populations in peripheral blood, and their roles have mostly been discussed in inflammation and autoimmunity. However, the functions of DNT cells in tumor microenvironment remain to be elucidated. We investigated their characteristics, possible origins and functions in colorectal cancer tissues as well as their corresponding tumor-draining lymph nodes. We found a significant enrichment of DNT cells in tumor tissues compared with their corresponding lymph nodes, especially in tumors with lower T cell infiltration. T cell receptor (TCR) sequence analysis of CD4+ T, CD8+ T and DNT cells indicated that TCR sequences detected in DNT cells were found in CD8+ T cells, but rarely in CD4+ T cells, suggesting that a part of DNT cells was likely to be originated from CD8+ T cells. Through a single-cell transcriptomic analysis of DNT cells, we found that a DNT cell cluster, which showed similar phenotypes to central memory CD8+ T cells with low expression of effector and exhaustion markers, revealed some specific gene expression patterns, including higher GZMK expression. Moreover, in flow cytometry analysis, we found that DNT cells lost production of cytotoxic mediators. These findings imply that DNT cells might function as negative regulators of anti-tumor immune responses in tumor microenvironment.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"13 1","pages":"2373530"},"PeriodicalIF":6.5,"publicationDate":"2024-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11229752/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141560114","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":"Cytokine release syndrome after treatment with immune checkpoint inhibitors: an observational cohort study of 2672 patients from Karolinska University Hospital in Sweden.","authors":"Osama Hamida, Frans Karlsson, Andreas Lundqvist, Marco Gerling, Lisa L Liu","doi":"10.1080/2162402X.2024.2372875","DOIUrl":"10.1080/2162402X.2024.2372875","url":null,"abstract":"<p><p>Immune checkpoint inhibitors (ICIs) are linked to diverse immune-related adverse events (irAEs). Rare irAEs surface first in clinical practice. Here, we systematically studied the rare irAE, cytokine-release syndrome (CRS), in a cohort of 2672 patients treated with ICIs at Karolinska University Hospital in Stockholm, Sweden. We find that the risk of ICI-induced CRS - defined as fever, negative microbiological findings and absence of other probable causes within 30 days after ICI treatment - is approximately 1%, higher than previously reported. ICI-induced CRS was often mild and rechallenge with ICIs after mild CRS was generally safe. However, two out of 28 patients experienced high-grade CRS, and one was fatal. While C-reactive protein (CRP) and procalcitonin were not discriminative of fatal CRS, our data suggest that the quick Sequential Organ Failure Assessment (qSOFA) score might identify high-risk patients. These data provide a framework for CRS risk assessment and motivate multicenter studies to improve early CRS diagnosis.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"13 1","pages":"2372875"},"PeriodicalIF":6.5,"publicationDate":"2024-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11225914/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141555756","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":"<i>Faecalibaterium prausnitzii</i> strain EXL01 boosts efficacy of immune checkpoint inhibitors.","authors":"Marius Bredon, Camille Danne, Hang Phuong Pham, Pauline Ruffié, Alban Bessede, Nathalie Rolhion, Laura Creusot, Loic Brot, Iria Alonso, Philippe Langella, Lisa Derosa, Alexis B Cortot, Bertrand Routy, Laurence Zitvogel, Nicola Segata, Harry Sokol","doi":"10.1080/2162402X.2024.2374954","DOIUrl":"10.1080/2162402X.2024.2374954","url":null,"abstract":"<p><p>Gut microbiota impacts responses to immune checkpoint inhibitors (ICI). A high level of <i>Faecalibacterium prausnitzii</i> have been associated with a positive response to ICI in multiple cancer types. Here, based on fecal shotgun metagenomics data, we show in two independent cohorts of patients with non-small cell lung cancer and advanced melanoma that a high level of <i>F. prausnitzii</i> at baseline is positively associated with a better clinical response to ICI. In MCA205 tumor-bearing mice, administration of <i>F.</i> <i>prausnitzii</i> strain EXL01, already in clinical development for Inflammatory Bowel Disease, restores the anti-tumor response to ICI in the context of antibiotic-induced microbiota perturbation at clinical and tumor transcriptomics level. In vitro, EXL01 strain enhances T cell activation in the presence of ICI. Interestingly, oral administration of EXL01 strain did not induce any change in fecal microbiota diversity or composition, suggesting a direct effect on immune cells in the small intestine. <i>F. prausnitzii</i> strain EXL01 will be evaluated as an adjuvant to ICI in multiple cancers in the near future.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"13 1","pages":"2374954"},"PeriodicalIF":6.5,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11218805/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141493992","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":"Complete response of metastatic microsatellite-stable <i>BRAF</i> V600E colorectal cancer to first-line oxaliplatin-based chemotherapy and immune checkpoint blockade.","authors":"Anne Hansen Ree, Eirik Høye, Ying Esbensen, Ann-Christin R Beitnes, Anne Negård, Linn Bernklev, Linn Kruse Tetlie, Åsmund A Fretland, Hanne M Hamre, Christian Kersten, Eva Hofsli, Marianne G Guren, Halfdan Sorbye, Hilde L Nilsen, Kjersti Flatmark, Sebastian Meltzer","doi":"10.1080/2162402X.2024.2372886","DOIUrl":"10.1080/2162402X.2024.2372886","url":null,"abstract":"<p><p>The randomized METIMMOX trial (NCT03388190) examined if patients with previously untreated, unresectable abdominal metastases from microsatellite-stable (MSS) colorectal cancer (CRC) might benefit from potentially immunogenic, short-course oxaliplatin-based chemotherapy alternating with immune checkpoint blockade (ICB). Three of 38 patients assigned to this experimental treatment had metastases from <i>BRAF</i>-mutant MSS-CRC, in general a poor-prognostic subgroup explored here. The ≥70-year-old females presented with ascending colon adenocarcinomas with intermediate tumor mutational burden (6.2-11.8 mutations per megabase). All experienced early disappearance of the primary tumor followed by complete response of all overt metastatic disease, resulting in progression-free survival as long as 20-35 months. However, they encountered recurrence at previously unaffected sites and ultimately sanctuary organs, or as intrahepatic tumor evolution reflected in the terminal loss of initially induced T-cell clonality in liver metastases. Yet, the remarkable first-line responses to short-course oxaliplatin-based chemotherapy alternating with ICB may offer a novel therapeutic option to a particularly hard-to-treat MSS-CRC subgroup.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"13 1","pages":"2372886"},"PeriodicalIF":6.5,"publicationDate":"2024-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11216098/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141477757","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":"Candidate tumor-specific CD8⁺ T cell subsets identified in the malignant pleural effusion of advanced lung cancer patients by single-cell analysis.","authors":"Yusuke Sugita, Daisuke Muraoka, Ayako Demachi-Okamura, Hiroyasu Komuro, Katsuhiro Masago, Eiichi Sasaki, Yasunori Fukushima, Takuya Matsui, Shuichi Shinohara, Yusuke Takahashi, Reina Nishida, Chieko Takashima, Teppei Yamaguchi, Yoshitsugu Horio, Kana Hashimoto, Ichidai Tanaka, Hiroshi Hamana, Hiroyuki Kishi, Daiki Miura, Yuki Tanaka, Kousuke Onoue, Kazuhide Onoguchi, Yoshiko Yamashita, Richard Stratford, Trevor Clancy, Rui Yamaguchi, Hiroaki Kuroda, Hironori Ishibashi, Kenichi Okubo, Hirokazu Matsushita","doi":"10.1080/2162402X.2024.2371556","DOIUrl":"10.1080/2162402X.2024.2371556","url":null,"abstract":"<p><p>Isolation of tumor-specific T cells and their antigen receptors (TCRs) from malignant pleural effusions (MPE) may facilitate the development of TCR-transduced adoptive cellular immunotherapy products for advanced lung cancer patients. However, the characteristics and markers of tumor-specific T-cells in MPE are largely undefined. To this end, to establish the phenotypes and antigen specificities of CD8⁺ T cells, we performed single-cell RNA and TCR sequencing of samples from three advanced lung cancer patients. Dimensionality reduction on a total of 4,983 CD8⁺ T cells revealed 10 clusters including naïve, memory, and exhausted phenotypes. We focused particularly on exhausted T cell clusters and tested their TCR reactivity against neoantigens predicted from autologous cancer cell lines. Four different TCRs specific for the same neoantigen and one orphan TCR specific for the autologous cell line were identified from one of the patients. Differential gene expression analysis in tumor-specific T cells relative to the other T cells identified <i>CXCL13</i>, as a candidate gene expressed by tumor-specific T cells. In addition to expressing <i>CXCL13</i>, tumor-specific T cells were present in a higher proportion of T cells co-expressing <i>PDCD1</i>(PD-1)/<i>TNFRSF9</i>(4-1BB). Furthermore, flow cytometric analyses in advanced lung cancer patients with MPE documented that those with high PD-1/4-1BB expression have a better prognosis in the subset of 57 adenocarcinoma patients (<i>p</i> = .039). These data suggest that PD-1/4-1BB co-expression might identify tumor-specific CD8⁺ T cells in MPE, which are associated with patients' prognosis. (233 words).</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"13 1","pages":"2371556"},"PeriodicalIF":6.5,"publicationDate":"2024-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11216099/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141477755","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":"Novel mRNA adjuvant ImmunER enhances prostate cancer tumor-associated antigen mRNA therapy via augmenting T cell activity.","authors":"Zhen Xu, Ze-Xiu Xiao, Jing Wang, Hao-Wei Qiu, Fei Cao, Shi-Qiang Zhang, Yuan-Dong Xu, Han-Qi Lei, Heng Xia, Yun-Ru He, Gao-Feng Zha, Jun Pang","doi":"10.1080/2162402X.2024.2373526","DOIUrl":"10.1080/2162402X.2024.2373526","url":null,"abstract":"<p><p>Prostate cancer (PCa) is characterized as a \"cold tumor\" with limited immune responses, rendering the tumor resistant to immune checkpoint inhibitors (ICI). Therapeutic messenger RNA (mRNA) vaccines have emerged as a promising strategy to overcome this challenge by enhancing immune reactivity and significantly boosting anti-tumor efficacy. In our study, we synthesized Tetra, an mRNA vaccine mixed with multiple tumor-associated antigens, and ImmunER, an immune-enhancing adjuvant, aiming to induce potent anti-tumor immunity. ImmunER exhibited the capacity to promote dendritic cells (DCs) maturation, enhance DCs migration, and improve antigen presentation at both cellular and animal levels. Moreover, Tetra, in combination with ImmunER, induced a transformation of bone marrow-derived dendritic cells (BMDCs) to cDC1-CCL22 and up-regulated the JAK-STAT1 pathway, promoting the release of IL-12, TNF-α, and other cytokines. This cascade led to enhanced proliferation and activation of T cells, resulting in effective killing of tumor cells. In vivo experiments further revealed that Tetra + ImmunER increased CD8⁺T cell infiltration and activation in RM-1-PSMA tumor tissues. In summary, our findings underscore the promising potential of the integrated Tetra and ImmunER mRNA-LNP therapy for robust anti-tumor immunity in PCa.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"13 1","pages":"2373526"},"PeriodicalIF":6.5,"publicationDate":"2024-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11212567/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141471773","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":"CD161⁺CD127⁺CD8⁺ T cell subsets can predict the efficacy of anti-PD-1 immunotherapy in non-small cell lung cancer with diabetes mellitus.","authors":"Jingjing Qu, Yuekang Li, Binggen Wu, Qian Shen, Lijun Chen, Wenjia Sun, Bo Wang, Lixiong Ying, Li Wu, Hong Zhou, Jianya Zhou, Jianying Zhou","doi":"10.1080/2162402X.2024.2371575","DOIUrl":"10.1080/2162402X.2024.2371575","url":null,"abstract":"<p><p>The role of CD161⁺CD127⁺CD8⁺ T cells in non-small cell lung cancer (NSCLC) patients with diabetes remains unexplored. This study determined the prevalence, phenotype, and function of CD8⁺ T cell subsets in NSCLC with diabetes. We recruited NSCLC patients (<i>n</i> = 436) treated with anti-PD-1 immunotherapy as first-line treatment. The progression-free survival (PFS), overall survival (OS), T cells infiltration, and peripheral blood immunological characteristics were analyzed in NSCLC patients with or without diabetes. NSCLC patients with diabetes exhibited shorter PFS and OS (<i>p</i> = 0.0069 and <i>p</i> = 0.012, respectively) and significantly lower CD8⁺ T cells infiltration. Mass cytometry by time-of-flight (CyTOF) showed a higher percentage of CD161⁺CD127⁺CD8⁺ T cells among CD8⁺T cells in NSCLC with diabetes before anti-PD-1 treatment (<i>p</i> = 0.0071) than that in NSCLC without diabetes and this trend continued after anti-PD-1 treatment (<i>p</i> = 0.0393). Flow cytometry and multiple-immunofluorescence confirmed that NSCLC with diabetes had significantly higher CD161⁺CD127⁺CD8⁺ T cells to CD8⁺T cells ratios than NSCLC patients without diabetes. The RNA-sequencing analysis revealed immune-cytotoxic genes were reduced in the CD161⁺CD127⁺CD8⁺ T cell subset compared to CD161⁺CD127^-CD8⁺ T cells in NSCLC with diabetes. CD161⁺CD127⁺CD8⁺ T cells exhibited more T cell-exhausted phenotypes in NSCLC with diabetes. NSCLC patients with diabetes with ≥ 6.3% CD161⁺CD127⁺CD8⁺ T cells to CD8⁺T cells ratios showed worse PFS. These findings indicate that diabetes is a risk factor for NSCLC patients who undergo anti-PD-1 immunotherapy.CD161⁺CD127⁺CD8⁺ T cells could be a key indicator of a poor prognosis in NSCLC with diabetes. Our findings would help in advancing anti-PD-1 therapy in NSCLC patients with diabetes.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"13 1","pages":"2371575"},"PeriodicalIF":6.5,"publicationDate":"2024-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11216103/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141477756","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}