Cancer immunology research最新文献_第9页

Reduced Tumor Control in Males Can Result from Impaired CD4+ T-cell Help through the CD40L-CD40 Pathway. 男性肿瘤控制减少可能是由于CD4+ t细胞通过CD40L-CD40途径帮助受损。

IF 7.9 1区医学

Cancer immunology research Pub Date : 2026-07-02 DOI: 10.1158/2326-6066.CIR-25-1115

Katey S Hunt, Samantha Cooke, Lindsey M Kuehm, Tyson A Lobb, Emily Ebert, Smrithi Beeram, Ryan M Teague, Michelle Brennan, Melissa M Berrien-Elliott, Stephen T Ferris, Elise Alspach

{"title":"Reduced Tumor Control in Males Can Result from Impaired CD4+ T-cell Help through the CD40L-CD40 Pathway.","authors":"Katey S Hunt, Samantha Cooke, Lindsey M Kuehm, Tyson A Lobb, Emily Ebert, Smrithi Beeram, Ryan M Teague, Michelle Brennan, Melissa M Berrien-Elliott, Stephen T Ferris, Elise Alspach","doi":"10.1158/2326-6066.CIR-25-1115","DOIUrl":"10.1158/2326-6066.CIR-25-1115","url":null,"abstract":"Sex-based differences in cancer incidence are incompletely understood, but potential roles for the immune system are beginning to emerge. CD4+ T cells play a central role in coordinating antitumor immunity. In addition to cytokine production, CD40L expression on CD4+ T cells provides necessary helper signaling to dendritic cells (DC) that is required for the priming of cytotoxic tumor-specific CD8+ T cells. Despite these critical functions, the impact of biological sex on the CD4+ T-cell response to cancer remains unknown. In this study, we demonstrate that impaired immune-mediated tumor control in male mice compared with female mice is driven by disparate CD4+ T-cell responses in a mouse model of bladder cancer. We found that CD40L expression was reduced on CD4+ T cells isolated from males via a mechanism predominantly driven by cell-intrinsic androgen receptor signaling, resulting in decreased DC licensing through CD40 within tumor-draining lymph nodes. These deficits resulted in decreased helper CD4+ T-cell frequencies and impaired CD8+ T-cell function within the male tumor microenvironment, which could be rescued by targeting the CD40L-CD40 axis. Our findings identify a novel mechanism of CD4+ T cell-based sex differences in the immune response to cancer that impairs tumor control. See related Spotlight, p. 1052.","PeriodicalId":9474,"journal":{"name":"Cancer immunology research","volume":" ","pages":"1068-1079"},"PeriodicalIF":7.9,"publicationDate":"2026-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13122763/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147509860","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Potent Cytotoxic Tumor-Infiltrating Lymphocytes Can Be Generated from Immune-Excluded Chondrosarcomas Using Regulatable Membrane-Bound IL15. 利用可调节的膜结合il - 15可以从免疫排斥的软骨肉瘤中产生有效的细胞毒性肿瘤浸润淋巴细胞。

IF 7.9 1区医学

Cancer immunology research Pub Date : 2026-06-02 DOI: 10.1158/2326-6066.CIR-25-1016

Zheng Ao, Rusul Al-Marayaty, Bulent Arman Aksoy, Farres Obeidin, Rachel Burga, Samer Attar, Terrance Peabody, Pedro Hermida de Viveiros, Juliana Chi Kei Ng, Weiqing Jing, Himaly Shinglot, Ali Zhang, Alonso Villasmil Ocando, Nishita Roy, Gauri Kulkarni, Andres Alvarado, Dexue Sun, Dhruv K Sethi, Michelle Ols, Jan Ter Meulen, Seth M Pollack

{"title":"Potent Cytotoxic Tumor-Infiltrating Lymphocytes Can Be Generated from Immune-Excluded Chondrosarcomas Using Regulatable Membrane-Bound IL15.","authors":"Zheng Ao, Rusul Al-Marayaty, Bulent Arman Aksoy, Farres Obeidin, Rachel Burga, Samer Attar, Terrance Peabody, Pedro Hermida de Viveiros, Juliana Chi Kei Ng, Weiqing Jing, Himaly Shinglot, Ali Zhang, Alonso Villasmil Ocando, Nishita Roy, Gauri Kulkarni, Andres Alvarado, Dexue Sun, Dhruv K Sethi, Michelle Ols, Jan Ter Meulen, Seth M Pollack","doi":"10.1158/2326-6066.CIR-25-1016","DOIUrl":"10.1158/2326-6066.CIR-25-1016","url":null,"abstract":"Autologous tumor-infiltrating lymphocyte (TIL) cell therapy is showing promising efficacy against immunologically \"hot\" tumors such as melanoma, cervical cancer, and renal cancer. However, generation of tumoricidal TILs from \"cold\" tumors with a low tumor mutational burden, such as many sarcoma types, poses a challenge due to limited infiltration of the tumor microenvironment (TME) with lymphocytes, low frequencies of tumor antigen-specific, high-affinity T cells, and incompletely understood mechanisms of immune-resistance prevailing in the TME. Here, we report the successful generation and expansion of TILs engineered with regulatable, membrane-bound IL15 (cytoTIL15 cells) from immune-excluded, paucicellular chondrosarcoma biopsies largely consisting of collagenous matrix and demonstrate that these cells have potent tumor-killing capacity in cell culture and in tumor spheroid models in the absence of exogenous IL2. Comprehensive spatial profiling of the TME revealed ubiquitous collagen and myeloid infiltration as major resistance mechanisms, whereas lymphocytic infiltration was largely restricted to peripheral regions of the tumors, a relevant consideration when sampling these tumors for TIL harvest. Moreover, we demonstrate that IL15 reduced the signaling threshold of T-cell receptors isolated from TIL clonotypes, increasing their infiltration and cytotoxicity in autologous 3D tumor models. These results suggest the possibility of developing an effective IL2-free TIL therapy for patients with immune-excluded tumors.","PeriodicalId":9474,"journal":{"name":"Cancer immunology research","volume":" ","pages":"944-957"},"PeriodicalIF":7.9,"publicationDate":"2026-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13227094/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146257622","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Capturing and Tracking Clonal T-cell Response to Cancer Neoantigens. 捕获和跟踪克隆T细胞对癌症新抗原的反应。

IF 8.2 1区医学

Cancer immunology research Pub Date : 2026-06-02 DOI: 10.1158/2326-6066.CIR-24-1216

Irina A Shagina, Tatyana O Nakonechnaya, Anna V Izosimova, Alexandra V Shabalkina, Diana V Yuzhakova, Valeriia D Skatova, Kseniia R Lupyr, Ilnar Muftakhutdinov, Mark Izraelson, Alexey N Davydov, Daniil Luppov, Mikhail Shugay, Olga V Britanova, Dmitry M Chudakov, George V Sharonov

{"title":"Capturing and Tracking Clonal T-cell Response to Cancer Neoantigens.","authors":"Irina A Shagina, Tatyana O Nakonechnaya, Anna V Izosimova, Alexandra V Shabalkina, Diana V Yuzhakova, Valeriia D Skatova, Kseniia R Lupyr, Ilnar Muftakhutdinov, Mark Izraelson, Alexey N Davydov, Daniil Luppov, Mikhail Shugay, Olga V Britanova, Dmitry M Chudakov, George V Sharonov","doi":"10.1158/2326-6066.CIR-24-1216","DOIUrl":"10.1158/2326-6066.CIR-24-1216","url":null,"abstract":"In humans and mice, the T-cell receptor (TCR) of each effector/memory T-cell clone recognizes one to several cognate peptide-MHC complexes (pMHC). Limited knowledge of TCR repertoire specificities restricts our capacity to rationally interpret this information, both diagnostically and in preclinical research. In this study, we (i) developed and validated a cost-efficient wet lab and computational pipeline to identify mouse TCRs specific to particular peptides, (ii) produced a dataset of helper T cell (Th) TCR beta chain CDR3s specific to B16 melanoma neoantigens in the I-Ab pMHCII context, available in VDJdb, and (iii) applied this dataset to track tumor-specific T-cell responses to the CTLA4 blocking immunotherapy in the orthotopic B16 melanoma model. We showed that B16-specific TCR motifs expanded in both Th and regulatory T cell (Treg) repertoires of tumor-bearing mice, with stronger expansion in the Th subset of mice treated with the CTLA4 blocking antibody. The response was stochastic across individual mice with respect to the specific TCR motifs and target peptides involved-each mouse displayed a unique response pattern, likely reflecting the natural diversity of molecular pathways underlying antitumor immunity. We also showed that CTLA4 blockade promotes prominent Th clonal expansion and induces general, nontumor-specific Th-to-Treg plasticity. Altogether, we provide a universal pipeline for the investigation of mouse T-cell responses at the antigen-specific level, facilitating the development and validation of immunotherapeutic and vaccination approaches.","PeriodicalId":9474,"journal":{"name":"Cancer immunology research","volume":" ","pages":"1022-1034"},"PeriodicalIF":8.2,"publicationDate":"2026-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147472762","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

FOXM1-Specific TCR-Engineered T Cells Target Non-Small Cell Lung Cancer. foxm1特异性tcr工程T细胞靶向非小细胞肺癌。

IF 7.9 1区医学

Cancer immunology research Pub Date : 2026-06-02 DOI: 10.1158/2326-6066.CIR-25-0605

Emily Bontekoe, Minying Zhang, Peixin Jiang, Amanda Montoya, Yulia Shulga, Jared K Slone, Emily Paul, Christopher Polera, Sarah Forward, Barbara Nassif Rausseo, Emane Rose Assita, Changsheng Xing, David P Molkentine, Benjamin B Morris, Isabella Polic, Janos Roszik, Ricardo Salgado, Aria Vaishnavi, Drew Deniger, Hai T Tran, Don L Gibbons, Ara Vaporciyan, Maura L Gillison, Ignacio I Wistuba, Lydia E Kavraki, Jianjun Zhang, Gregory Lizee, Cassian Yee, Patrick Hwu, Sheldon Kwok, Alex M Jaeger, John V Heymach, Alexandre Reuben

{"title":"FOXM1-Specific TCR-Engineered T Cells Target Non-Small Cell Lung Cancer.","authors":"Emily Bontekoe, Minying Zhang, Peixin Jiang, Amanda Montoya, Yulia Shulga, Jared K Slone, Emily Paul, Christopher Polera, Sarah Forward, Barbara Nassif Rausseo, Emane Rose Assita, Changsheng Xing, David P Molkentine, Benjamin B Morris, Isabella Polic, Janos Roszik, Ricardo Salgado, Aria Vaishnavi, Drew Deniger, Hai T Tran, Don L Gibbons, Ara Vaporciyan, Maura L Gillison, Ignacio I Wistuba, Lydia E Kavraki, Jianjun Zhang, Gregory Lizee, Cassian Yee, Patrick Hwu, Sheldon Kwok, Alex M Jaeger, John V Heymach, Alexandre Reuben","doi":"10.1158/2326-6066.CIR-25-0605","DOIUrl":"10.1158/2326-6066.CIR-25-0605","url":null,"abstract":"FOXM1 is highly expressed in various cancer types and considered a key driver of cancer progression. Accordingly, we evaluated the immunogenicity of FOXM1 and investigated the feasibility of targeting this transcription factor using T-cell receptor (TCR) engineering. We identified epitopes derived from FOXM1 which were immunogenic on HLA-A*02:01, HLA-A*24:02, and HLA-A*23:01, endogenously processed and presented, and resulted in T-cell activation and cytotoxic T-cell responses. Following the generation of TCR-T cells, sensitivity and specificity were confirmed by peptide dose-response and X-scan, respectively. Most importantly, adoptive transfer of TCR-engineered T cells led to a significant reduction in tumor growth, as well as significantly prolonged survival in a tumor-bearing immunocompromised murine model. Our studies confirm the immunogenicity of FOXM1 and feasibility of targeting this antigen using TCR engineering.","PeriodicalId":9474,"journal":{"name":"Cancer immunology research","volume":" ","pages":"958-973"},"PeriodicalIF":7.9,"publicationDate":"2026-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13119620/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147484785","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Targeted TNF Potentiates the Activity of Bispecific T-cell Engagers in Solid Tumors by Turning Cold Tumors Hot. 靶向TNF通过使冷肿瘤变热来增强实体肿瘤中双特异性t细胞接合物的活性。

IF 8.2 1区医学

Cancer immunology research Pub Date : 2026-06-02 DOI: 10.1158/2326-6066.CIR-25-1572

Gudrun Thorhallsdottir, Ramon Benz, Pinuccia Faviana, Francesco Bartoli, Natascia Leonardi, Ivann Sekielyk, Laura Fetriconi, Samuele Cazzamalli, Emanuele Puca, Dario Neri, Abdullah Elsayed

{"title":"Targeted TNF Potentiates the Activity of Bispecific T-cell Engagers in Solid Tumors by Turning Cold Tumors Hot.","authors":"Gudrun Thorhallsdottir, Ramon Benz, Pinuccia Faviana, Francesco Bartoli, Natascia Leonardi, Ivann Sekielyk, Laura Fetriconi, Samuele Cazzamalli, Emanuele Puca, Dario Neri, Abdullah Elsayed","doi":"10.1158/2326-6066.CIR-25-1572","DOIUrl":"10.1158/2326-6066.CIR-25-1572","url":null,"abstract":"Colorectal cancer remains a major global health burden and an area of urgent unmet medical need. Immunotherapy has shown limited success in colorectal cancer as most patients present with an immune-excluded, \"cold\" tumor microenvironment (TME). In this study, we report a dual-modality approach to treating colorectal cancer by combining the tumor necrosis factor (TNF)-based fusion protein directed to the extradomain B (EDB) of fibronectin, L19-TNF, which induces localized intratumoral inflammation and facilitates T-cell infiltration, with a CD3-based bispecific T-cell engager (TCE) targeting carcinoembryonic antigen (CEA), which mediates antigen-specific cytotoxicity. Together, these agents aim to remodel the TME, convert \"cold\" tumors into inflamed \"hot\" lesions, and broaden the therapeutic reach of immunotherapy in colorectal cancer. Immunohistochemistry confirmed coexpression of CEA and EDB across microsatellite-stable and -instable tumors. In vitro, L19-TNF in combination with a CEAxCD3 TCE significantly enhanced tumor cell killing and CD8+ T-cell proliferation. In vivo, the combination induced complete tumor regression in most animals, prolonged survival, and conferred durable protection against tumor rechallenge. Furthermore, mechanistic analyses revealed enhanced TCE extravasation, upregulated intercellular adhesion molecule 1 expression, and increased CD8+ T-cell infiltration, indicating vascular modulation and remodeling of the TME toward an inflamed \"hot\" phenotype. These findings confirm that targeted delivery of TNF to the TME can effectively enhance the activity of immunotherapeutic agents, such as T cell-redirecting therapies, in challenging tumor settings.","PeriodicalId":9474,"journal":{"name":"Cancer immunology research","volume":" ","pages":"919-932"},"PeriodicalIF":8.2,"publicationDate":"2026-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147763223","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

DDR1 Promotes Immune Evasion in Colorectal Cancer by Orchestrating IL33-Mediated M2-like Polarization of Tumor-Associated Macrophages. DDR1通过协调il -33介导的肿瘤相关巨噬细胞的m2样极化促进结直肠癌的免疫逃避。

IF 7.9 1区医学

Cancer immunology research Pub Date : 2026-06-02 DOI: 10.1158/2326-6066.CIR-25-1073

Xiaofan Duan, Gaoshaer Yeerkenbieke, Yanjun Feng, Mingwang Zhou, Yumei Zhang, Jiuli Zhou, Jin Li

{"title":"DDR1 Promotes Immune Evasion in Colorectal Cancer by Orchestrating IL33-Mediated M2-like Polarization of Tumor-Associated Macrophages.","authors":"Xiaofan Duan, Gaoshaer Yeerkenbieke, Yanjun Feng, Mingwang Zhou, Yumei Zhang, Jiuli Zhou, Jin Li","doi":"10.1158/2326-6066.CIR-25-1073","DOIUrl":"10.1158/2326-6066.CIR-25-1073","url":null,"abstract":"Colorectal cancer remains a leading cause of cancer-related mortality, with low immunotherapy efficacy due to an immunosuppressive tumor microenvironment in proficient mismatch repair (pMMR) disease, which accounts for most cases of colorectal cancer. In this study, we have identified discoidin domain receptor 1 (DDR1) as a key immune evasion driver in syngeneic tumor models. Moreover, intestine-specific Ddr1 knockout (KO) suppressed tumorigenesis in azoxymethane/dextran sulfate sodium and ApcMin/+ mouse models of colorectal cancer, with reduced frequency of M2-like tumor-associated macrophages (TAM) and increased infiltration of CD8+ T cells. Mechanistically, DDR1 induced p-c-Jun-dependent IL33 transcription to drive M2-like macrophage polarization. Mass spectrometry and immunoprecipitation analyses further revealed that DDR1 interacted with DExD-box helicase 21 (DDX21) in the nucleus, which inhibited DDX21 ubiquitination, increasing DDX21 levels, which subsequently enhanced c-Jun phosphorylation. Clinically, elevated DDR1 expression in patients with colorectal cancer correlated with poor prognosis and was positively associated with DDX21 and p-c-Jun. Furthermore, both DDR1 and DDX21 expression showed positive correlations with M2-like TAM infiltration in patient tissues. Therapeutically, genetic KO and nanoparticle-delivered siRNA targeting DDR1 significantly enhanced anti-PD-1 treatment efficacy in vivo. Thus, our findings establish DDR1-DDX21-c-Jun-IL33 as an axis that drives immunosuppression in colorectal cancer by regulating TAM polarization and indicate DDR1 as a potential target to improve immunotherapy efficacy in pMMR patients.","PeriodicalId":9474,"journal":{"name":"Cancer immunology research","volume":" ","pages":"900-918"},"PeriodicalIF":7.9,"publicationDate":"2026-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13227095/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147653794","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Integrated Single-Cell Profiling Reveals Dichotomous NK Cell Populations Associated with Immunosuppression in Solid Tumors. 综合单细胞分析揭示与实体肿瘤免疫抑制相关的两种NK细胞群。

IF 7.9 1区医学

Cancer immunology research Pub Date : 2026-06-02 DOI: 10.1158/2326-6066.CIR-25-1229

John R Lozada, Atef Ali, Christine Luo, Rosemary N Plagens, Bin Zhang, Andrew Elliott, Ella Boytim, Nicholas A Zorko, Elisabeth I Heath, Akash Patnaik, Ari M VanderWalde, Emmanuel S Antonarakis, Jeffrey S Miller, Justin H Hwang, Frank Cichocki

{"title":"Integrated Single-Cell Profiling Reveals Dichotomous NK Cell Populations Associated with Immunosuppression in Solid Tumors.","authors":"John R Lozada, Atef Ali, Christine Luo, Rosemary N Plagens, Bin Zhang, Andrew Elliott, Ella Boytim, Nicholas A Zorko, Elisabeth I Heath, Akash Patnaik, Ari M VanderWalde, Emmanuel S Antonarakis, Jeffrey S Miller, Justin H Hwang, Frank Cichocki","doi":"10.1158/2326-6066.CIR-25-1229","DOIUrl":"10.1158/2326-6066.CIR-25-1229","url":null,"abstract":"Natural killer (NK) cells represent key effectors of antitumor immunity, yet emerging evidence highlights populations with distinct roles in cancer. Despite such expanded diversity within the NK cell repertoire, we lack an understanding of how this heterogeneity affects immune responses and downstream clinical outcomes. Using single-cell RNA sequencing, we systematically profiled NK cells across cancer and uncovered a dichotomous phenotypic and functional landscape of tumor-infiltrating NK cells shaped by opposing intrinsic signaling programs that drive the expression of IFNG or TGFB1. These divergent programs are associated with distinct transcription factor circuits that integrate cues within the tumor microenvironment and skew NK cells toward proinflammatory or suppressive functions. We found that the capacity for NK cells to engage in either functional direction is intrinsically linked to their phenotypic identity. Canonical NK cells recruited from circulation predominantly directed suppressive TGFB1 signals toward effector CD8+ T cells in tumors. Of note, these subsets exhibited higher TGFB1 expression than intratumoral myeloid cells across tumor types. In contrast, a tissue-resident (TR) adaptive subset exhibited exclusively proinflammatory IFNG-driven profiles and was associated with prolonged survival in both primary and metastatic tumor settings. Moreover, these TR adaptive NK cells, but not other subsets, were linked to response to immune checkpoint blockade. Collectively, our study reveals a previously unrecognized regulatory axis in NK cells that shapes NK cell diversity and augments broader antitumor immune responses.","PeriodicalId":9474,"journal":{"name":"Cancer immunology research","volume":" ","pages":"1008-1021"},"PeriodicalIF":7.9,"publicationDate":"2026-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13063350/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147316230","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

HTRA1+ Macrophages Induce T-cell Egress through CRIP1/NF-κB/CXCL12 to Limit the Effects of Immunotherapy in Triple-Negative Breast Cancer. HTRA1+巨噬细胞通过CRIP1/NF-κB/CXCL12诱导T细胞的分泌，限制免疫治疗对三阴性乳腺癌的影响。

IF 8.2 1区医学

Cancer immunology research Pub Date : 2026-06-02 DOI: 10.1158/2326-6066.CIR-25-1138

Jialei Weng, Wenxin Xu, Fu Wang, Liqian Zhao, Feng Ju, Rongyue Teng, Di Wu, Lixi Luo, Yabing Du, Yifan Wang, Zhiqiang Hu, Heming Zheng

{"title":"HTRA1+ Macrophages Induce T-cell Egress through CRIP1/NF-κB/CXCL12 to Limit the Effects of Immunotherapy in Triple-Negative Breast Cancer.","authors":"Jialei Weng, Wenxin Xu, Fu Wang, Liqian Zhao, Feng Ju, Rongyue Teng, Di Wu, Lixi Luo, Yabing Du, Yifan Wang, Zhiqiang Hu, Heming Zheng","doi":"10.1158/2326-6066.CIR-25-1138","DOIUrl":"10.1158/2326-6066.CIR-25-1138","url":null,"abstract":"The variation in immunotherapy responses among patients with triple-negative breast cancer (TNBC) is attributed to the high heterogeneity of tumor immune components, in which macrophages play a key role. Hence, identification of key macrophage subpopulations associated with immunotherapy efficacy could provide important biological and therapeutic insights. In this study, using single-cell and spatial transcriptomes, we identified, at the single-cell level, a subpopulation of macrophages related to T-cell expansion during immunotherapy, characterized by high expression of high-temperature requirement A1 (HTRA1), and correlated with clinical and immunotherapy outcomes in TNBC. Loss of macrophage-specific Htra1 in transgenic mice resulted in delayed TNBC growth, improved immunotherapy efficacy, and increased CD8+ T-cell infiltration. Mechanistically, HTRA1 associated with cysteine-rich protein 1 (CRIP1) to facilitate CRIP1 binding to NF-κB, thereby activating the NF-κB pathway and downstream CXCL12 transcription, leading to T-cell exit from tumors. Endothelial cell-derived CX3CL1 was implicated in the recruitment of HTRA1+ macrophages to tumor sites. Pharmacologic antagonism of the CXCL12/CXCR4 axis potentiated the immunotherapy efficacy in orthotopic TNBC mouse models. In conclusion, this study highlights an HTRA1+ macrophage subpopulation that can limit T-cell infiltration and immunotherapy efficacy via the CXCL12/CXCR4 axis, which offers new leads to improve immunotherapeutic interventions in TNBC.","PeriodicalId":9474,"journal":{"name":"Cancer immunology research","volume":" ","pages":"992-1007"},"PeriodicalIF":8.2,"publicationDate":"2026-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147484828","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Induction Serplulimab and Chemotherapy Followed by Chemoradiotherapy for Bulky Unresectable Stage III NSCLC: A Phase II Study (SUCCEED-01). 诱导serpluliumab和化疗后放化疗治疗大体积不可切除的III期NSCLC：一项II期研究（成功-01）。

IF 7.9 1区医学

Cancer immunology research Pub Date : 2026-06-02 DOI: 10.1158/2326-6066.CIR-25-1194

Chengxin Liu, Yang Du, Dan Han, Baosheng Li, Xiaomeng Liu, Bingjie Fan, Hongfu Sun, Chengrui Fu, Longyu Xu, Tianyuan Dai, Wei Huang

{"title":"Induction Serplulimab and Chemotherapy Followed by Chemoradiotherapy for Bulky Unresectable Stage III NSCLC: A Phase II Study (SUCCEED-01).","authors":"Chengxin Liu, Yang Du, Dan Han, Baosheng Li, Xiaomeng Liu, Bingjie Fan, Hongfu Sun, Chengrui Fu, Longyu Xu, Tianyuan Dai, Wei Huang","doi":"10.1158/2326-6066.CIR-25-1194","DOIUrl":"10.1158/2326-6066.CIR-25-1194","url":null,"abstract":"Patients with bulky, unresectable stage III non-small cell lung cancer (NSCLC) face poor outcomes with standard concurrent chemoradiotherapy (cCRT) due to large radiation fields and toxicity risks. We evaluated the feasibility and efficacy of induction immunochemotherapy to downstage tumors prior to cCRT. In this single-arm, phase II study, eligible patients received two cycles of induction serplulimab plus chemotherapy. Patients without progression underwent multidisciplinary restaging to receive either cCRT with serplulimab consolidation or surgery. The primary endpoints were objective response rate (ORR) after cCRT and changes in lung volume receiving ≥20 Gy (V20). Forty-nine patients were enrolled (75.5% stage IIIB/IIIC). Following induction, the V20 value was significantly reduced by 11.41% (P < 0.001). The ORR following cCRT was 77.14% (95% confidence interval, 59.86%-89.58%). The 12-month progression-free survival and overall survival rates were 76.15% and 90.54%, respectively. Notably, six patients successfully underwent R0 resection, with five achieving a pathologic complete response. Grade 3 adverse events occurred in 14.29% of patients, and toxicities were manageable. Induction serplulimab-chemotherapy prior to cCRT is a promising strategy for bulky, stage III NSCLC. This approach significantly reduced radiation volumes, achieved high response rates, and enabled curative surgery in selected patients with manageable toxicity.","PeriodicalId":9474,"journal":{"name":"Cancer immunology research","volume":" ","pages":"1035-1044"},"PeriodicalIF":7.9,"publicationDate":"2026-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13227087/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147580445","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A Sampling of Highlights from the Literature: Article Recommendations from Our Deputy and Senior Editors. 从文献的亮点抽样：文章推荐从我们的副和高级编辑。

IF 7.9 1区医学

Cancer immunology research Pub Date : 2026-06-02 DOI: 10.1158/2326-6066.CIR-14-6-WWR

引用次数: 0