Douglas C Chung, Noor Shakfa, Jehan Vakharia, Kathrin Warner, Nicolas Jacquelot, Azin Sayad, SeongJun Han, Maryam Ghaedi, Carlos R Garcia-Batres, Jules Sotty, Arvin Azarmina, Ferris Nowlan, Edward L Y Chen, Michael Zon, Alisha R Elford, Ben X Wang, Linh T Nguyen, Miralem Mrkonjic, Blaise A Clarke, Marcus Q Bernardini, Benjamin Haibe-Kains, Sarah E Ferguson, Sarah Q Crome, Hartland W Jackson, Pamela S Ohashi
{"title":"CD103+CD56+ ILCs Are Associated with an Altered CD8+ T-cell Profile within the Tumor Microenvironment.","authors":"Douglas C Chung, Noor Shakfa, Jehan Vakharia, Kathrin Warner, Nicolas Jacquelot, Azin Sayad, SeongJun Han, Maryam Ghaedi, Carlos R Garcia-Batres, Jules Sotty, Arvin Azarmina, Ferris Nowlan, Edward L Y Chen, Michael Zon, Alisha R Elford, Ben X Wang, Linh T Nguyen, Miralem Mrkonjic, Blaise A Clarke, Marcus Q Bernardini, Benjamin Haibe-Kains, Sarah E Ferguson, Sarah Q Crome, Hartland W Jackson, Pamela S Ohashi","doi":"10.1158/2326-6066.CIR-24-0151","DOIUrl":"10.1158/2326-6066.CIR-24-0151","url":null,"abstract":"<p><p>Immunotherapies have had unprecedented success in the treatment of multiple cancer types, albeit with variable response rates. Unraveling the complex network of immune cells within the tumor microenvironment (TME) may provide additional insights to enhance antitumor immunity and improve clinical response. Many studies have shown that NK cells or innate lymphoid cells (ILC) have regulatory capacity. Here, we identified CD103 as a marker that was found on CD56+ cells that were associated with a poor proliferative capacity of tumor-infiltrating lymphocytes in culture. We further demonstrated that CD103+CD56+ ILCs isolated directly from tumors represented a distinct ILC population that expressed unique surface markers (such as CD49a and CD101), transcription factor networks, and transcriptomic profiles compared with CD103-CD56+ NK cells. Using single-cell multiomic and spatial approaches, we found that these CD103+CD56+ ILCs were associated with CD8+ T cells with reduced expression of granzyme B. Thus, this study identifies a population of CD103+CD56+ ILCs with potentially inhibitory functions that are associated with a TME that includes CD8+ T cells with poor antitumor activity. Further studies focusing on these cells may provide additional insights into the biology of an inhibitory TME.</p>","PeriodicalId":9474,"journal":{"name":"Cancer immunology research","volume":" ","pages":"527-546"},"PeriodicalIF":8.1,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11962407/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143623803","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}
Paula I Gonzalez-Ericsson, Susan R Opalenik, Violeta Sanchez, Amy M Palubinsky, Ann Hanna, Xiaopeng Sun, Andres A Ocampo, Guadalupe Garcia, Leonel Maldonado, Zaida Morante, Tatiana Vidaurre, Guillermo Valencia, Henry L Gomez, Melinda E Sanders, Laura C Kennedy, Elizabeth J Phillips, Justin M Balko
{"title":"In Situ Detection of Individual Classic MHC-I Gene Products in Cancer.","authors":"Paula I Gonzalez-Ericsson, Susan R Opalenik, Violeta Sanchez, Amy M Palubinsky, Ann Hanna, Xiaopeng Sun, Andres A Ocampo, Guadalupe Garcia, Leonel Maldonado, Zaida Morante, Tatiana Vidaurre, Guillermo Valencia, Henry L Gomez, Melinda E Sanders, Laura C Kennedy, Elizabeth J Phillips, Justin M Balko","doi":"10.1158/2326-6066.CIR-24-1003","DOIUrl":"10.1158/2326-6066.CIR-24-1003","url":null,"abstract":"<p><p>Tumor-specific HLA class I expression is required for cytotoxic T-cell elimination of cancer cells expressing tumor-associated antigens or neoantigens. Cancers downregulate antigen presentation to avoid adaptive immunity. The highly polymorphic nature of the genes encoding these proteins, coupled with quaternary-structure changes after formalin fixation, complicates detection by IHC. In this study, we determined recognition of 16 specific HLA-A, -B, and -C alleles by 15 antibodies commercially available for IHC use, identifying and validating pan and specific HLA-A, -B, and -C antibodies, providing a validated method that can be applied to investigate HLA-A, -B, and -C molecule-specific loss in cancer. We applied this approach to a series of breast cancers as a proof of utility, identifying differential HLA-A, -B, and -C loss, with a higher incidence of HLA-A and -B loss in hormone-driven breast cancers, HLA-B loss in HER2+ cancers, and an equal loss of all three molecules in triple-negative disease. Additionally, we found that at the protein level, HLA-A and -B loss were early events prevalent in premalignant lesions, whereas HLA-C loss was less common throughout tumor evolution. Effective response to immunotherapies such as checkpoint inhibitors and MHC-I-targeted cancer vaccines, which hinge on the carriage of specific allele groups, requires MHC-I expression on tumor cells. These findings have implications for the success of checkpoint inhibitors and vaccine strategies.</p>","PeriodicalId":9474,"journal":{"name":"Cancer immunology research","volume":" ","pages":"602-609"},"PeriodicalIF":8.1,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142969016","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}
Matthew D Galsky, Mark Kockx, Juliette Roels, Roos Van Elzen, Xiangnan Guan, Kobe Yuen, Deepali Rishipathak, Jonathan F Anker, Sacha Gnjatic, Sudeh Izadmehr, Shomyseh Sanjabi, Robert J Johnston, Maureen Peterson, Hartmut Koeppen, Justin M David, Saurabh Gupta, Aristotelis Bamias, Jose Angel Arranz, Eiji Kikuchi, Maria De Santis, Ian D Davis, Patrick Williams, Sandrine Bernhard, Ira Mellman, Enrique Grande, Romain Banchereau, Sanjeev Mariathasan
{"title":"Different PD-L1 Assays Reveal Distinct Immunobiology and Clinical Outcomes in Urothelial Cancer.","authors":"Matthew D Galsky, Mark Kockx, Juliette Roels, Roos Van Elzen, Xiangnan Guan, Kobe Yuen, Deepali Rishipathak, Jonathan F Anker, Sacha Gnjatic, Sudeh Izadmehr, Shomyseh Sanjabi, Robert J Johnston, Maureen Peterson, Hartmut Koeppen, Justin M David, Saurabh Gupta, Aristotelis Bamias, Jose Angel Arranz, Eiji Kikuchi, Maria De Santis, Ian D Davis, Patrick Williams, Sandrine Bernhard, Ira Mellman, Enrique Grande, Romain Banchereau, Sanjeev Mariathasan","doi":"10.1158/2326-6066.CIR-24-0649","DOIUrl":"10.1158/2326-6066.CIR-24-0649","url":null,"abstract":"<p><p>Testing for PD-L1 expression by IHC is used to predict immune checkpoint blockade (ICB) benefits but has performed inconsistently in urothelial cancer clinical trials. Different approaches are used for PD-L1 IHC. We analyzed paired PD-L1 IHC data on urothelial cancer samples using the SP142 and 22C3 assays from the phase III IMvigor130 trial and found discordant findings summarized by four phenotypes: PD-L1 positive by both assays, PD-L1 positive by the SP142 assay only, PD-L1 positive by the 22C3 assay only, and PD-L1 negative by both assays double negative. PD-L1 positive by both assays and PD-L1 positive by the SP142 assay only urothelial cancers were associated with more favorable ICB outcomes and increased dendritic cell (DC) infiltration. SP142 PD-L1 staining co-localized with DC-LAMP, a DC marker, whereas 22C3 staining was more diffuse. PD-L1 positive by the 22C3 assay only urothelial cancers, associated with worse outcomes, were enriched in tumor cell (TC)-dominant PD-L1 expression. Multiplex IHC in an independent ICB-treated cohort confirmed that TC-dominant PD-L1 expression was associated with shorter survival. Using different PD-L1 assays, we uncovered that SP142 may preferentially stain PD-L1-expressing DCs, key to orchestrating antitumor immunity, whereas TC-dominant PD-L1 expression, which underlies a subset of \"PD-L1-positive\" specimens, is associated with poor ICB outcomes. See related Spotlight by Karunamurthy and Davar, p. 454 .</p>","PeriodicalId":9474,"journal":{"name":"Cancer immunology research","volume":" ","pages":"476-486"},"PeriodicalIF":8.1,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11962399/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143032314","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}
{"title":"There and back again: PD-L1 Positivity as a Biomarker for Immune Checkpoint Blockade in Urothelial Carcinoma.","authors":"Arivarasan Karunamurthy, Diwakar Davar","doi":"10.1158/2326-6066.CIR-25-0202","DOIUrl":"10.1158/2326-6066.CIR-25-0202","url":null,"abstract":"<p><p>Biomarkers of responsiveness to immune checkpoint blockade (ICB) are heavily sought given the breadth and depth of the use of ICB in cancer. PD-L1 expression was among the first biomarkers identified, but multiple factors have precluded more widespread use. In this issue, Galsky and colleagues utilize two separate PD-L1 assays to study urothelial carcinoma specimens and observe that SP142 (relative to 22C3) preferentially stains dendritic cells. These observations may help reconcile the discordant performance of the two PD-L1 assays in ICB-treated urothelial carcinoma while underscoring the role of dendritic cells in orchestrating ICB response. See related article by Galsky et al., p. 476 .</p>","PeriodicalId":9474,"journal":{"name":"Cancer immunology research","volume":" ","pages":"454-455"},"PeriodicalIF":8.1,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143623804","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}
Emily Schwarz, Himanshu Savardekar, Sara Zelinskas, Abigail Mouse, Gabriella Lapurga, Justin Lyberger, Adithe Rivaldi, Emily M Ringwalt, Katherine E Miller, Lianbo Yu, Gregory K Behbehani, Timothy P Cripe, William E Carson
{"title":"Trabectedin Enhances the Antitumor Effects of IL-12 in Triple-Negative Breast Cancer.","authors":"Emily Schwarz, Himanshu Savardekar, Sara Zelinskas, Abigail Mouse, Gabriella Lapurga, Justin Lyberger, Adithe Rivaldi, Emily M Ringwalt, Katherine E Miller, Lianbo Yu, Gregory K Behbehani, Timothy P Cripe, William E Carson","doi":"10.1158/2326-6066.CIR-24-0775","DOIUrl":"10.1158/2326-6066.CIR-24-0775","url":null,"abstract":"<p><p>IL-12 is a potent NK cell-stimulating cytokine, but the presence of immunosuppressive myeloid cells such as myeloid-derived suppressor cells (MDSC) can inhibit IL-12-induced NK-cell cytotoxicity. Thus, we hypothesized that trabectedin, a myeloid cell-depleting agent, would improve the efficacy of IL-12 in triple-negative breast cancer (TNBC). In vitro treatment of healthy donor NK cells with trabectedin increased expression of the activation marker CD69 and mRNA expression of T-box transcription factor (Tbx21), the cytotoxic ligands TNF-related apoptosis-inducing ligand (TNFSF10), Fas ligand (FASLG), and the dendritic cell (DC)-recruiting chemokine lymphotactin (XCL1). The combination of IL-12 and trabectedin increased NK-cell cytotoxicity and activation and production of IFN-γ, TNF-α, and granzyme B in the presence of human TNBC cells. Treatment of 4T1 and EMT6 tumor-bearing mice with IL-12 and trabectedin led to a significant reduction in tumor burden compared with single-agent controls and the highest levels of plasma IFN-γ, intratumoral CD8+ T cells, and conventional type 1 DC. MDSC and M2-like macrophages were significantly decreased with combination therapy. NK-cell depletion abrogated the effects of combination therapy, as did the elimination of CD8+ T cells. NK-cell depletion led to lower levels of the NK cell-derived chemokine CCL5 and the DC-derived chemokine CXCL10, higher tumor burden, and decreased intratumoral CD8+ T cells. IL-12 and trabectedin also significantly enhanced the response of TNBC to anti-PD-L1 therapy. These data suggest that MDSC depletion augments the ability of IL-12-activated NK cells to drive the infiltration of DC and CD8+ T cells into TNBC for an antitumor effect.</p>","PeriodicalId":9474,"journal":{"name":"Cancer immunology research","volume":" ","pages":"560-576"},"PeriodicalIF":8.1,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11962391/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142945100","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}
{"title":"Profiling Multiple CD8+ T-cell Functional Dimensions Enhances Breast Cancer Immune Assessment.","authors":"Zhuozhi Liang, Shunrong Li, Zhilong Pan, Yuanqiang Duan, Qian Ouyang, Liling Zhu, Erwei Song, Kai Chen","doi":"10.1158/2326-6066.CIR-24-0235","DOIUrl":"10.1158/2326-6066.CIR-24-0235","url":null,"abstract":"<p><p>CD8+ T-cell abundance is insufficient to assess antitumor immunity and shows poor performance in predicting breast cancer prognosis and immunotherapy response, presumably owing to the complexity of CD8+ T-cell functionalities. Although single-cell RNA sequencing can dissect the multifaceted functions of CD8+ T cells for better immune assessment, its clinical application is limited. In this study, we developed bulk RNA sequencing-based FuncDimen models from integrative analysis of single-cell RNA sequencing and matched bulk RNA sequencing data to evaluate CD8+ T-cell functionalities across five dimensions: tumor reactivity, cytotoxicity, IFNγ secretion, proliferation, and apoptosis. The FuncDimen models quantifying different functional dimensions of CD8+ T cells were validated in our breast cancer cohort and external databases using immunofluorescence and imaging mass cytometry. We calculated the FuncAggre score by weighted aggregation of all five FuncDimen models to encapsulate the overall antitumor immunity. In our breast cancer cohort and external databases, the FuncAggre score demonstrated superior predictive performance for breast cancer prognosis (time-dependent AUC: 0.56-0.70) and immunotherapy response (AUC: 0.71-0.83) over other immune biomarkers, regardless of the breast cancer molecular subtype. Together, the FuncDimen models offer a refined assessment of antitumor immunity mediated by CD8+ T cells in the clinic, enhancing prognostic prediction and aiding personalized immunotherapy in breast cancer.</p>","PeriodicalId":9474,"journal":{"name":"Cancer immunology research","volume":" ","pages":"337-352"},"PeriodicalIF":8.1,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142881448","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}
Yaiza Senent, Ana Remírez, David Repáraz, Diana Llopiz, Daiana P Celias, Cristina Sainz, Rodrigo Entrialgo-Cadierno, Lucia Suarez, Ana Rouzaut, Diego Alignani, Beatriz Tavira, John D Lambris, Trent M Woodruff, Carlos E de Andrea, Brian Ruffell, Pablo Sarobe, Daniel Ajona, Ruben Pio
{"title":"The C5a/C5aR1 Axis Promotes Migration of Tolerogenic Dendritic Cells to Lymph Nodes, Impairing the Anticancer Immune Response.","authors":"Yaiza Senent, Ana Remírez, David Repáraz, Diana Llopiz, Daiana P Celias, Cristina Sainz, Rodrigo Entrialgo-Cadierno, Lucia Suarez, Ana Rouzaut, Diego Alignani, Beatriz Tavira, John D Lambris, Trent M Woodruff, Carlos E de Andrea, Brian Ruffell, Pablo Sarobe, Daniel Ajona, Ruben Pio","doi":"10.1158/2326-6066.CIR-24-0250","DOIUrl":"10.1158/2326-6066.CIR-24-0250","url":null,"abstract":"<p><p>The precise mechanisms by which the complement system contributes to the establishment of an immunosuppressive tumor microenvironment and promotes tumor progression remain unclear. In this study, we investigated the expression and function of complement C5a receptor 1 (C5aR1) in human and mouse cancer-associated dendritic cells (DC). First, we observed an overexpression of C5aR1 in tumor-infiltrating DCs, compared with DCs from the blood or spleen. C5aR1 expression was restricted to type 2 conventional DCs and monocyte-derived DCs, which displayed a tolerogenic phenotype capable of inhibiting T-cell activation and promoting tumor growth. C5aR1 engagement in DCs drove their migration from tumors to tumor-draining lymph nodes, where C5a levels were higher. We used this knowledge to optimize an anticancer therapy aimed at enhancing DC activity. In three syngeneic tumor models, C5aR1 inhibition significantly enhanced the efficacy of poly I:C, a Toll-like receptor 3 agonist, in combination with PD-1/PD-L1 blockade. The contribution of C5aR1 inhibition to the antitumor activity of the combination treatment relied on type 1 conventional DCs and antigen-specific CD8+ T cells, required lymphocyte egress from secondary lymphoid organs, and was associated with an increase in IFNγ signaling. In conclusion, our study highlights the importance of the C5a/C5aR1 axis in the biology of cancer-associated DCs and provides compelling evidence for the therapeutic potential of modulating the complement system to enhance DC-mediated immune responses against tumors.</p>","PeriodicalId":9474,"journal":{"name":"Cancer immunology research","volume":" ","pages":"384-399"},"PeriodicalIF":8.1,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142812115","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}
{"title":"Mathematical Modeling Predicts Optimal Immune Checkpoint Inhibitor and Radiotherapy Combinations and Timing of Administration.","authors":"Shunsuke A Sakai, Koichi Saeki, SungGi Chi, Yamato Hamaya, Junyan Du, Masaki Nakamura, Hidehiro Hojo, Takashi Kojima, Yoshiaki Nakamura, Hideaki Bando, Motohiro Kojima, Ayako Suzuki, Yutaka Suzuki, Tetsuo Akimoto, Katsuya Tsuchihara, Hiroshi Haeno, Riu Yamashita, Shun-Ichiro Kageyama","doi":"10.1158/2326-6066.CIR-24-0610","DOIUrl":"10.1158/2326-6066.CIR-24-0610","url":null,"abstract":"<p><p>Radiotherapy (RT) combined with immune checkpoint inhibitor (ICI) therapy has attracted substantial attention due to its potential to improve outcomes for patients with several types of cancer. However, the optimal administration timepoints and drug combinations remain unclear because the mechanisms underlying RT-induced changes in immune checkpoint molecule expression and interaction with their ligand(s) remain unclear. In this study, we demonstrated the dynamics of lymphocyte-mediated molecular interactions in tissue samples from patients with esophageal cancer throughout RT schedules. Single-cell RNA sequencing and spatial transcriptomic analyses were performed to investigate the dynamics of these interactions. The biological signal in lymphocytes transitioned from innate to adaptive immune reaction, with increases in ligand-receptor interactions, such as PD-1-PD-L1, CTLA4-CD80/86, and TIGIT-PVR interactions. A mathematical model was constructed to predict the efficacy of five types of ICIs when administered at four different timepoints. The model suggested that concurrent anti-PD-1/PD-L1 therapy or concurrent/adjuvant anti-CTLA4/TIGIT therapy would exert a maximal effect with RT. This study provides rationale for clinical trials of RT combined with defined ICI therapy, and these findings will support future studies to search for more effective targets and timing of therapy administration.</p>","PeriodicalId":9474,"journal":{"name":"Cancer immunology research","volume":" ","pages":"353-364"},"PeriodicalIF":8.1,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11876959/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142812114","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}
{"title":"A Sampling of Highlights from the Literature.","authors":"","doi":"10.1158/2326-6066.CIR-13-3-WWR","DOIUrl":"https://doi.org/10.1158/2326-6066.CIR-13-3-WWR","url":null,"abstract":"","PeriodicalId":9474,"journal":{"name":"Cancer immunology research","volume":"13 3","pages":"309"},"PeriodicalIF":8.1,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143540232","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}
Jonas Lehmann, Martin Thelen, Christoph Kreer, Simon Schran, Maria A Garcia-Marquez, Igor Cisic, Klara Siepmann, Elena M Hagen, Hans Nikolaus Caspar Eckel, Philipp Lohneis, Stephan Kruger, Stefan Boeck, Steffen Ormanns, Martina Rudelius, Jens Werner, Felix Popp, Florian Klein, Michael S von Bergwelt-Baildon, Christiane J Bruns, Alexander Quaas, Kerstin Wennhold, Hans A Schlößer
{"title":"Tertiary Lymphoid Structures in Pancreatic Cancer are Structurally Homologous, Share Gene Expression Patterns and B-cell Clones with Secondary Lymphoid Organs, but Show Increased T-cell Activation.","authors":"Jonas Lehmann, Martin Thelen, Christoph Kreer, Simon Schran, Maria A Garcia-Marquez, Igor Cisic, Klara Siepmann, Elena M Hagen, Hans Nikolaus Caspar Eckel, Philipp Lohneis, Stephan Kruger, Stefan Boeck, Steffen Ormanns, Martina Rudelius, Jens Werner, Felix Popp, Florian Klein, Michael S von Bergwelt-Baildon, Christiane J Bruns, Alexander Quaas, Kerstin Wennhold, Hans A Schlößer","doi":"10.1158/2326-6066.CIR-24-0299","DOIUrl":"10.1158/2326-6066.CIR-24-0299","url":null,"abstract":"<p><p>Tertiary lymphoid structures (TLS) in cancer are considered ectopic hotspots for immune activation that are similar to lymphoid follicles in secondary lymphoid organs (SLO). This study elucidates shared and TLS/SLO-specific features in pancreatic ductal adenocarcinoma (PDAC). TLS abundance was related to superior survival and T-cell abundance in 110 treatment-naïve PDAC samples, underlining their clinical relevance. Immunofluorescence microscopy identified structural homologies between TLSs and SLOs. In RNA expression analyses of laser-microdissected TLSs and paired SLOs, we observed largely overlapping expression patterns of immune-related gene clusters but distinct expression patterns of T-cell and complement-associated genes. Immune cells in TLS expressed essential markers of germinal center formation. Increased activation of tumor-draining lymph nodes in patients with high numbers of TLSs highlights the relevance of these tumor-related structures to systemic immune response. In line with this, we identified an overlap of expanded B-cell receptor clonotypes in TLSs and SLOs, which suggests a vivid cross-talk between the two compartments. We conclude that combined therapeutic approaches exploiting TLS-mediated antitumor immune responses may improve susceptibility of PDAC to immunotherapy.</p>","PeriodicalId":9474,"journal":{"name":"Cancer immunology research","volume":" ","pages":"323-336"},"PeriodicalIF":8.1,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142805902","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}
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
