Cancer Immunology, Immunotherapy最新文献

{"title":"In situ treatment with a TLR9 agonist virus-like particle to promote immune responses against oral epithelial dysplasia progression.","authors":"Yan Xu, Alexandra Mcmillan, Nikesh Gupta, Caitlin D Lemke-Miltner, Aseel O Rataan, Sudartip Areecheewakul, Divya S Bhat, Emily A Lanzel, Sean M Geary, Andrean L Simons, George J Weiner, Aliasger K Salem","doi":"10.1007/s00262-025-04023-1","DOIUrl":"10.1007/s00262-025-04023-1","url":null,"abstract":"<p><p>Leukoplakia, a common type of oral dysplasia, is simply defined as a white patch in the mouth or other mucosal surface. Oral dysplasia is the most common premalignancy in the oral cavity and yet it is insufficiently researched and thus both diagnosing and treating oral dysplasia are still problematic issues. This study focuses on the immune signature of oral dysplasia and explores whether stimulating the immune system with an immune therapy, vidutolimod (± immune checkpoint blockade (ICB)), can prevent the progression of oral dysplasia or even cause regression. Vidutolimod, a virus-like particle encapsulating G10, is believed to activate plasmacytoid dendritic cells (pDCs) through the activation of the Toll-like receptor 9 (TLR9). To investigate this, an established murine model for inducing oral cancer was used to study oral dysplasia development and response to in situ injection of vidutolimod at the premalignant phase. The effect of treatment was analyzed histologically and immunologically. ELISA revealed significantly elevated levels of IFN-γ, IL-12, and TNF-α in the sera of mice after 24 h of one treatment with vidutolimod + ICB as well as increased levels of proliferating T cells and pDCs in draining lymph nodes 72 h after the third and final treatment, thus indicating the immune-boosting effect of this therapy. Vidutolimod + ICB caused a significant decrease in Ki-67 expression by epithelial cells in the lesion area compared to untreated mice, implicating that this treatment regime may prevent lesion progression.</p>","PeriodicalId":9595,"journal":{"name":"Cancer Immunology, Immunotherapy","volume":"74 6","pages":"189"},"PeriodicalIF":4.6,"publicationDate":"2025-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12049351/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143977503","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":"Transcriptomic and proteomic characterization of cell and protein biomarkers of checkpoint inhibitor-induced liver injury.","authors":"Changhua Ji, Steven Kumpf, Jessie Qian, Joel D Federspiel, Mark Sheehan, Darien Capunitan, Edmond Atallah, Stuart Astbury, Seda Arat, Elias Oziolor, Mireia Fernandez Ocana, Shashi K Ramaiah, Jane Grove, Guruprasad P Aithal, Thomas A Lanz","doi":"10.1007/s00262-025-04033-z","DOIUrl":"10.1007/s00262-025-04033-z","url":null,"abstract":"<p><p>Immune checkpoint inhibitors (ICI) targeting CTLA-4 and PD-1 have shown remarkable antitumor efficacy, but can also cause immune-related adverse events, including checkpoint inhibitor-induced liver injury (ChILI). This multi-omic study aimed to investigate changes in blood samples from treated cancer patients who developed ChILI. PBMCs were sequenced for by transcriptomic and T cell receptor repertoire (bulk and single-cell immune profiling), and extracellular vesicle (EV) enrichment from plasma was analyzed by mass spectroscopy proteomics. Data were analyzed by comparing the ChILI patient group to the control group who did not develop ChILI and by comparing the onset of ChILI to pre-ICI treatment baseline. We identified significant changes in T cell clonality, gene expression, and proteins in peripheral blood mononuclear cells (PBMCs) and plasma in response to liver injury. Onset of ChILI was accompanied by an increase in T cell clonality. Pathway analysis highlighted the involvement of innate and cellular immune responses, mitosis, pyroptosis, and oxidative stress. Single-cell RNA sequencing revealed that these changes were primarily found in select T cell subtypes (including CD8 + effector memory cells), while CD16 + monocytes exhibited enrichment in metabolic pathways. Proteomic analysis of plasma extracellular vesicles showed enrichment in liver-associated proteins among differentially expressed proteins. Interestingly, an increase in PBMC PD-L1 gene expression and plasma PD-L1 protein was also found to be associated with ChILI onset. These findings provide valuable insights into the immune and molecular mechanisms underlying ChILI as well as potential biomarkers of ChILI.Trial registration number NCT04476563.</p>","PeriodicalId":9595,"journal":{"name":"Cancer Immunology, Immunotherapy","volume":"74 6","pages":"190"},"PeriodicalIF":4.6,"publicationDate":"2025-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12049347/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143977228","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":"GD2-CAR NK-92 cell activity against neuroblastoma cells is insusceptible to TIGIT knockout.","authors":"Wiebke Jünemann, Isabelle Bley, Laura Rekowski, Marianne Klokow, Susanne Herppich, Ingo Müller, Kerstin Cornils","doi":"10.1007/s00262-025-04010-6","DOIUrl":"10.1007/s00262-025-04010-6","url":null,"abstract":"<p><p>Immunotherapy by inhibition of immune checkpoint (IC) molecules has emerged as an important cancer therapy. Among these lC, the poliovirus receptor/poliovirus receptor-like 2 protein (PVR/PVRL2)-TIGIT axis was discovered as potential target for various cancers. For neuroblastoma (NB), the most common extracranial solid cancer in children, no effective IC therapy has been established yet. To investigate the PVR/PVRL2-TIGIT IC axis as a new target for the treatment of NB, we analysed whether PVR and PVRL2 influence the survival of patients and verified the expression of the receptors on NB cell lines. To disrupt the checkpoint axis, we performed single and double knockouts of these receptors on NB cell lines and subsequently removed TIGIT, an inhibitory receptor on immune effector cells, from NK-92 cells. Finally, we combined checkpoint inhibition with GD2-CAR NK-92 cells and investigated changes in cytotoxicity. Using RNA-Seq data we showed that the expression of PVR and PVRL2 on NB cells correlates to a lower event-free survival of patients. CRISPR/Cas9 knockouts of PVR and PVRL2 showed no improved cytotoxic activity of NK-92 cells. We observed enhanced lysis of NB cells using TIGIT-deficient NK-92 cells. However, the cytotoxicity of GD2-CAR NK-92 was not significantly enhanced. In summary, we have shown that in addition to the interaction of PVR/PVRL2 and TIGIT on engineered immune effector cells against NB, pleiotropic ligands appear to be relevant. Deletion of TIGIT from immune effector cells is a promising approach to protect these cells from tumour-associated inhibitory signals but cannot enhance the effect of GD2-CAR-NK-92 cells.</p>","PeriodicalId":9595,"journal":{"name":"Cancer Immunology, Immunotherapy","volume":"74 6","pages":"191"},"PeriodicalIF":4.6,"publicationDate":"2025-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12049354/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143968749","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: Antitumor effects of immunotherapy combined with BRAF and MEK inhibitors in BRAF V600E metastatic colorectal cancer.","authors":"Eunyoung Tak, Hye-In An, Amy Sinyoung Lee, Kyuyoung Han, Jiwan Choi, Hyung-Don Kim, Yong Sang Hong, Sun Young Kim, Eun Kyung Choi, Jeong Eun Kim, Tae Won Kim","doi":"10.1007/s00262-025-04056-6","DOIUrl":"10.1007/s00262-025-04056-6","url":null,"abstract":"","PeriodicalId":9595,"journal":{"name":"Cancer Immunology, Immunotherapy","volume":"74 6","pages":"187"},"PeriodicalIF":4.6,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12040781/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143980312","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":"Targeting interleukin-2-inducible T cell kinase ameliorates immune-mediated aplastic anemia.","authors":"Weiwang Li, Yu Lian, Lele Zhang, Ruonan Li, Qian Liang, Jin Mao, Chen Qiu, Haoyuan Li, Ke Huang, Qiaoli Li, Yucan Shen, Fei Yang, Linzhu Tian, Tingfang Xiao, Shilong Gu, Hong Pan, Zhen Gao, Jingyu Zhao, Liwei Fang, Meili Ge, Weiping Yuan, Yajing Chu, Jun Shi","doi":"10.1007/s00262-025-04040-0","DOIUrl":"10.1007/s00262-025-04040-0","url":null,"abstract":"<p><p>Allogeneic stem cell transplant and immunosuppressive therapy (IST) are the current standard treatments for patients with aplastic anemia (AA). However, IST also carries significant risks and side effects, and up to 30-50% of patients experienced refractory or relapsed disease following IST. Treating AA remains challenging and novel efficient therapies are in critical need. The IL-2 inducible T-cell kinase (ITK) plays a crucial role in the T cell response and functions as a regulator of T cell activity. While ITK inhibition has shown promise in various immune-related disorders, its potential role in the pathophysiology of AA has not been thoroughly investigated. We observed elevated level of phosphorylated ITK in T cells from AA patients and AA mouse models. Moreover, we found that both treatment with an ITK inhibitor or conditional depletion of Itk in donor mice alleviated bone marrow hypoplasia, improved cytopenia, and extended survival rates. Notably, ITK inhibition orchestrates T cell quantity and function by reducing T cell infiltration and suppressing the secretion of key inflammatory cytokines in AA mice. Our data suggest that ITK inhibitor could potentially offer a new therapeutic strategy for AA.</p>","PeriodicalId":9595,"journal":{"name":"Cancer Immunology, Immunotherapy","volume":"74 6","pages":"188"},"PeriodicalIF":4.6,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12040803/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143980220","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":"Cadonilimab, a PD-1/CTLA-4 bispecific antibody in unresectable hepatocellular carcinoma: a real-world study.","authors":"Yilin Wang, Shida Pan, Jiahe Tian, Jianing Wang, Yingying Yu, Siyu Wang, Fengyi Li, Luo Yang, Xiaomeng Liu, Yingjuan Shen, Qin Qiu, Junqing Luan, Mengdie Jia, Chuyue Xiong, Xuanxuan Duan, Fu-Sheng Wang, Fanping Meng","doi":"10.1007/s00262-025-04038-8","DOIUrl":"10.1007/s00262-025-04038-8","url":null,"abstract":"<p><strong>Objective: </strong>This study retrospectively evaluated the safety and efficacy of cadonilimab combined with tyrosine kinase inhibitors (TKI) for the treatment of unresectable hepatocellular carcinoma (uHCC).</p><p><strong>Patients and methods: </strong>Seventy-eight patients who received cadonilimab + TKI were included; 42 and 36 received it as first-line (1 L) and second-line and above (≥ 2 L) systemic treatment, respectively. Besides, ninety-five patients who received PD-1 inhibitor + TKI as first-line treatments were included. Safety was the primary endpoint; secondary endpoints were overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and disease control rate (DCR).</p><p><strong>Results: </strong>Treatment-related adverse events (TRAEs) of any grade occurred in 84.6% of the patients, with grade ≥ 3 in 20.5%. In patients with a Child-Pugh score of ≥ 8 (CP ≥ 8), any grade TRAEs occurred in 88.2%, and grade ≥ 3 in 20.6%. The overall cohort's median progression-free survival (mPFS) was 3.6 months, whereas the median overall survival (mOS) was 8.8 months. In the 1 L group, mPFS was 6.7 months versus 2.3 months in ≥ 2 L. In the 1 L group, mOS was 13.7 months versus 3.2 months in ≥ 2 L. For CP < 8, 1 L mPFS was 7.6 months, mOS not reached; CP ≥ 8 had mPFS of 5.2 months, mOS of 5.6 months. For CP < 8 in ≥ 2 L, mPFS was 3.1 months, mOS 8.8 months; CP ≥ 8 had mPFS of 1.4 months, mOS of 2.2 months. After propensity score matching (PSM), the incidence of TRAEs of any grade was 77.1%, with grade ≥ 3 accounting for 17.1% in the PD-1 group. In the PD-1/CTLA-4 group, the incidence of TRAEs of any grade was 80.0%, and that of grade ≥ 3 TRAEs was 17.1%. The mPFS was 6.7 months in the PD-1/CTLA-4 group versus 3.3 months in the PD-1 group. The mOS was 13.7 months in the PD-1/CTLA-4 group versus 6.7 months in the PD-1 group.</p><p><strong>Conclusion: </strong>Cadonilimab + TKI showed a favorable trend in safety and efficacy, especially when applied as first-line systemic therapy for uHCC. This study offers a clinical reference for its use in systemic uHCC therapy, particularly in patients with advanced liver dysfunction.</p>","PeriodicalId":9595,"journal":{"name":"Cancer Immunology, Immunotherapy","volume":"74 6","pages":"186"},"PeriodicalIF":4.6,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12037968/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143954767","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":"Multifaceted functions of tissue-resident memory T cells in tumorigenesis and cancer immunotherapy.","authors":"Eun Sang Seo, Sung-Kyu Lee, Young Min Son","doi":"10.1007/s00262-025-04035-x","DOIUrl":"10.1007/s00262-025-04035-x","url":null,"abstract":"<p><p>Tissue-resident memory T (T_RM) cells are well reported as a strong protective first line of defense against foreign antigens in non-lymphoid tissues. Moreover, T_RM cells have demonstrated critical protective roles in antitumor immunity, contributing to enhanced survival and tumor growth inhibition across various cancer types. However, surprisingly, recent studies suggest that T_RM cells can exhibit paradoxical effects, potentially promoting tumor progression under certain conditions and leading to adverse outcomes during antitumor immune responses. Understanding the complexities of T_RM cell functions will enable us to harness their potential in advancing cancer immunotherapy more effectively. Therefore, this review comprehensively investigates the dual roles of T_RM cells in different tumor contexts, highlighting their protective functions in combating cancers and their unfavorable potential to exacerbate tumor development. Additionally, we explore the implications of T_RM cell behaviors for future cancer treatment strategies, emphasizing the need for further research to optimize the therapeutic exploitation of T_RM cells while mitigating their deleterious effects.</p>","PeriodicalId":9595,"journal":{"name":"Cancer Immunology, Immunotherapy","volume":"74 6","pages":"184"},"PeriodicalIF":4.6,"publicationDate":"2025-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12033165/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143960890","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":"Dynamics of tertiary lymphoid structures and immune cross talk in early versus advanced colorectal cancer: potential implications for immunotherapy.","authors":"Zixu Chen, Bang Hu, Keyu Cai, Han Gao, Zhenyu Xian, Shuang Zhang, Zhen Fang, Qian Zhou, Donglin Ren, Qi Zou","doi":"10.1007/s00262-025-04027-x","DOIUrl":"10.1007/s00262-025-04027-x","url":null,"abstract":"<p><strong>Background: </strong>Irrespective of microsatellite status, immune checkpoint inhibitor therapy shows superior efficacy in early-stage colorectal cancer (CRC) compared to advanced cases. The distinctions of the tumor microenvironment (TME) and tertiary lymphoid structure (TLS) between early- and advanced-stage CRC may represent a critical factor, yet remain incompletely elucidated.</p><p><strong>Methods: </strong>We comprehensively analyzed single-cell RNA sequencing data, bulk RNA transcription data and pathological tissue data to investigate the dynamic changes in the TME. The features of TLS in early- and advanced-stage tumors and their potential impact on immunotherapy were explored using three in-house cohorts.</p><p><strong>Results: </strong>We provided single-cell fine maps of the immune landscape in early and advanced CRC. Significant functional differences were identified in CD4 + Tfh and BGC cells between early and advanced CRC. We revealed CXCL13 expression on CD8 + Tex cells, along with CD40-CD40L interactions between CD4 + Tfh and BGC cells, could be key regulators of TLS functionality and subsequently affect the response to immunotherapy.</p><p><strong>Conclusions: </strong>Our research shed light on the multilayered immune dysfunction in advanced CRC and elucidates the alterations in the TLS during the progression of CRC, providing insights for functional studies and the exploration of potential target in advanced CRC.</p>","PeriodicalId":9595,"journal":{"name":"Cancer Immunology, Immunotherapy","volume":"74 6","pages":"185"},"PeriodicalIF":4.6,"publicationDate":"2025-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12033131/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143966626","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":"Blockade of TIGAR prevents CD8⁺ T cell dysfunction and elicits anti-AML immunity.","authors":"Jialin Cui, Wenjie Liu, Shiyang Zhong, Yiran Fang, Pei Xu, Cheng Xu, Rong Wang, Xingfei Hu, Wanting Zhou, Kening Li, Ming Hong, Sixuan Qian, Qian Sun","doi":"10.1007/s00262-025-04042-y","DOIUrl":"10.1007/s00262-025-04042-y","url":null,"abstract":"<p><p>Acute myeloid leukemia (AML) cells and activated T cells rely on aerobic glycolysis for energy metabolism. The TP53-induced glycolysis and apoptosis regulator (TIGAR) inhibits glycolysis and protects AML cells from apoptosis. Preliminary studies suggest that combining TIGAR inhibition with the glycolysis inhibitor 2-deoxy-D-glucose (2-DG) may offer a therapeutic strategy for AML. However, it remains unclear whether silencing TIGAR can enhance T cell function and thereby improve AML prognosis. This study aims to investigate whether TIGAR silencing in host can eliminate AML cells and rejuvenate dysfunctional T cells with mouse models. TIGAR knockout mice on the C57BL/6J background were generated and AML mouse models were established through intravenous injection of C1498 cells. We found that TIGAR depletion enhanced CD8⁺ T cell counts and raised CD4/CD8 ratio, downregulating CD44 and immune checkpoints CTLA-4, LAG-3, PD-1 on cell surface of CD8⁺ T cells. TIGAR depletion boosted cytokine secretion (IFN-γ, perforin, granzyme B, TNF-α) by CD8⁺ T cells and IL-2, TNF-α by CD4⁺ T cells, improving cytotoxicity against AML cells, proliferation, and reducing apoptosis. TIGAR suppression in host with 2-DG prolonged AML mouse survival, decreased tumor burden, and leukemic infiltration. TIGAR suppression restored thymic T cell development and peripheral immune balance. Single-cell RNA sequencing analysis also revealed that high TIGAR expression influences the glycolysis pathway, and correlates with markers of T cell exhaustion. This study indicates that blocking TIGAR prevents CD8⁺ T cell dysfunction and induces anti-AML immunity.</p>","PeriodicalId":9595,"journal":{"name":"Cancer Immunology, Immunotherapy","volume":"74 6","pages":"183"},"PeriodicalIF":4.6,"publicationDate":"2025-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12033161/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143974864","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":"Expression of the TIGIT axis and the CD39/CD73 purinergic pathway in bone metastasis-derived immune cells.","authors":"Elias Brauneck, Leon-Gordian Leonhardt, Anne Marie Assemissen, Yagana Wahid, Moritz Kruppa, Niklas Kruppa, Julius Krüger, Stephan Menzel, Friedrich Koch-Nolte, Julian Kylies, Katja Weisel, Carsten Bokemeyer, Jasmin Wellbrock, Walter Fiedler, Lennart Viezens, Franziska Brauneck","doi":"10.1007/s00262-025-04030-2","DOIUrl":"10.1007/s00262-025-04030-2","url":null,"abstract":"<p><strong>Background: </strong>Bone metastases (BM) represent one of the most common sites of metastasis. The study aimed to compare the composition of immune cell infiltration from aspirates of different BM prior to systemic therapy.</p><p><strong>Method: </strong>Phenotypic and functional analyses were conducted via multiparametric flow cytometry (MFC) on BM-derived aspirates obtained from patients with breast cancer (BC, n = 6), patients with prostate cancer (PC, n = 5), patients with non-small-cell lung cancer (NSCLC) (n = 7), patients with myeloma (MM, n = 10) and bone aspirates from age-matched non-malignant controls (NMC, n = 10).</p><p><strong>Results: </strong>Across all tumors aspirates the fraction of CD8⁺ T cells was reduced. In contrast, infiltration by immunosuppressive CD56⁺CD16^-NK and CD163⁺CD86⁺ M2-like macrophages was increased in BM compared to NMC aspirates. BM-derived CD8⁺ T cells aberrantly co-expressed TIGIT with PVRIG or CD39. Similarly, BM-derived cytotoxic NK cells co-expressed TIGIT and PVRIG. In addition, BM-derived M2-like macrophages exhibited an increased subset of cells co-expressing either TIGIT and PVRL4 or CD112 and CD155. Using a myeloma model, functional in vitro studies showed that blockade of TIGIT and CD39 leads to increased PBMC-mediated lysis of myeloma cells.</p><p><strong>Conclusion: </strong>The study shows that an altered immune cell composition is present in BM across the different tumor entities. Additionally, molecules of the TIGIT checkpoint as well as of the purinergic pathway are aberrantly expressed by BM-infiltrating CD8⁺ T cells, NK cells and macrophages and also functionally relevant for tumor cell lysis.</p>","PeriodicalId":9595,"journal":{"name":"Cancer Immunology, Immunotherapy","volume":"74 6","pages":"182"},"PeriodicalIF":4.6,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12022200/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143984493","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}