Cancer immunology research最新文献

{"title":"NI-3201 Is a Bispecific Antibody Mediating PD-L1-Dependent CD28 Co-stimulation on T Cells for Enhanced Tumor Control.","authors":"Sara Majocchi, Pauline Lloveras, Lise Nouveau, Margaux Legrand, Alizee Viandier, Pauline Malinge, Maud Charreton, Cecile Raymond, Emily A Pace, Bjorn L Millard, L Anders Svensson, Vinardas Kelpšas, Nadia Anceriz, Susana Salgado-Pires, Bruno Daubeuf, Giovanni Magistrelli, Franck Gueneau, Valéry Moine, Krzysztof Masternak, Limin Shang, Nicolas Fischer, Walter G Ferlin","doi":"10.1158/2326-6066.CIR-24-0298","DOIUrl":"10.1158/2326-6066.CIR-24-0298","url":null,"abstract":"<p><p>Despite advances in cancer immunotherapy, such as targeting the PD-1/PD-L1 axis, a substantial number of patients harbor tumors that are resistant or relapse. Selective engagement of T-cell co-stimulatory molecules with bispecific antibodies may offer novel therapeutic options by enhancing signal 1-driven activation occurring via T-cell receptor engagement. In this study, we report the development and preclinical characterization of NI-3201, a PD-L1×CD28 bispecific antibody generated on the κλ-body platform that was designed to promote T-cell activity and antitumor function through a dual mechanism of action. We confirmed that NI-3201 blocks the PD-L1/PD-1 immune checkpoint pathway and conditionally provides T-cell co-stimulation via CD28 (signal 2) when engaging PD-L1+ tumors or immune cells. In systems with signal 1-primed T cells, NI-3201 enhanced potent effector functionality: in vitro through antigen-specific recall assays with cytomegalovirus-specific T cells and in vivo by inducing tumor regression and immunologic memory in tumor-associated antigen-expressing MC38 syngeneic mouse models. When T-cell engagers were used to provide synthetic signal 1, the combination with NI-3201 resulted in synergistic T cell-dependent cytotoxicity and potent antitumor activity in two humanized mouse tumor models. Nonhuman primate safety assessments showed favorable tolerability and pharmacokinetics at pharmacologically active doses. Quantitative systems pharmacology modeling predicted that NI-3201 exposure results in antitumor activity in patients, but this remains to be investigated. Overall, this study suggests that by combining PD-L1 blockade with safe and effective CD28 co-stimulation, NI-3201 has the potential to improve cancer immunotherapy outcomes, and the clinical development of NI-3201 for PD-L1+ solid tumors is planned.</p>","PeriodicalId":9474,"journal":{"name":"Cancer immunology research","volume":" ","pages":"365-383"},"PeriodicalIF":8.1,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11876958/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142930623","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":"Natural Killer Cell-Mediated Cytotoxicity Shapes the Clonal Evolution of B-cell Leukemia.","authors":"Michelle C Buri, Mohamed R Shoeb, Aleksandr Bykov, Peter Repiscak, Hayeon Baik, Alma Dupanovic, Faith O David, Boris Kovacic, Faith Hall-Glenn, Sara Dopa, Jos Urbanus, Lisa Sippl, Susanne Stofner, Dominik Emminger, Jason Cosgrove, Dagmar Schinnerl, Anna R Poetsch, Manfred Lehner, Xaver Koenig, Leïla Perié, Ton N Schumacher, Dagmar Gotthardt, Florian Halbritter, Eva M Putz","doi":"10.1158/2326-6066.CIR-24-0189","DOIUrl":"10.1158/2326-6066.CIR-24-0189","url":null,"abstract":"<p><p>The term cancer immunoediting describes the dual role by which the immune system can suppress and promote tumor growth and is divided into three phases: elimination, equilibrium, and escape. The role of NK cells has mainly been attributed to the elimination phase. Here, we show that NK cells play a role in all three phases of cancer immunoediting. Extended co-culturing of DNA-barcoded mouse BCR/ABLp185+ B-cell acute lymphoblastic leukemia (B-ALL) cells with NK cells allowed for a quantitative measure of NK cell-mediated immunoediting. Although most tumor cell clones were efficiently eliminated by NK cells, a certain fraction of tumor cells harbored an intrinsic primary resistance. Furthermore, DNA barcoding revealed tumor cell clones with secondary resistance, which stochastically acquired resistance to NK cells. NK cell-mediated cytotoxicity put a selective pressure on B-ALL cells, which led to an outgrowth of primary and secondary resistant tumor cell clones, which were characterized by an IFNγ signature. Besides well-known regulators of immune evasion, our analysis of NK cell-resistant tumor cells revealed the upregulation of genes, including lymphocyte antigen 6 complex, locus A (Ly6a), which we found to promote leukemic cell resistance to NK cells. Translation of our findings to the human system showed that high expression of LY6E on tumor cells impaired their physical interaction with NK cells and led to worse prognosis in patients with leukemia. Our results demonstrate that tumor cells are actively edited by NK cells during the equilibrium phase and use different avenues to escape NK cell-mediated eradication.</p>","PeriodicalId":9474,"journal":{"name":"Cancer immunology research","volume":" ","pages":"430-446"},"PeriodicalIF":8.1,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7617306/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142789615","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":"Spatial Organization of Macrophages in CTL-Rich Hepatocellular Carcinoma Influences CTL Antitumor Activity.","authors":"Yulan Weng, Lu Wang, Yuting Wang, Junyu Xu, Xiaoli Fan, Shufeng Luo, Qiaomin Hua, Jing Xu, Gaoteng Liu, Kai-Bo Zhao, Chang-An Zhao, Dong-Ming Kuang, Chong Wu, Limin Zheng","doi":"10.1158/2326-6066.CIR-24-0589","DOIUrl":"10.1158/2326-6066.CIR-24-0589","url":null,"abstract":"<p><p>Despite the pivotal role of CTLs in antitumor immunity, a substantial proportion of CTL-rich patients with hepatocellular carcinoma (HCC) experience early relapse or immunotherapy resistance. However, spatial immune variations impacting the heterogeneous clinical outcomes of CTL-rich HCCs remain poorly understood. In this study, we compared the single-cell and spatial landscapes of 20 CTL-rich HCCs with distinct prognoses using multiplexed in situ staining and validated the prognostic value of myeloid spatial patterns in a cohort of 386 patients. Random forest and Cox regression models identified macrophage aggregation as a distinctive spatial pattern characterizing a subset of CTL-rich HCCs with an immunosuppressive microenvironment and poor prognosis. Integrated analysis of single-cell and spatial transcriptomics, combined with in situ staining validation, revealed that spatial aggregation enhanced protumoral macrophage reprogramming in HCCs, marked by lipid metabolism orientation, M2-like polarization, and increased adjacent CTL exhaustion. This spatial effect on macrophage reprogramming was replicated in HCC-conditioned human macrophage cultures, which showed an enhanced capability to suppress CTLs. Notably, increased macrophage aggregation was associated with higher response rates to anti-PD-1 immunotherapy. These findings suggest that the spatial distribution of macrophages is a biomarker of their functional diversities and microenvironment status, which holds prognostic and therapeutic implications.</p>","PeriodicalId":9474,"journal":{"name":"Cancer immunology research","volume":" ","pages":"310-322"},"PeriodicalIF":8.1,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142913843","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":"The FcγRIIIA (CD16) L48-H/R Polymorphism Enhances NK Cell-Mediated Antibody-Dependent Cellular Cytotoxicity by Promoting Serial Killing.","authors":"Nicholas A Maskalenko, Sam Zahroun, Oxana Tsygankova, Nadia Anikeeva, Yuri Sykulev, Kerry S Campbell","doi":"10.1158/2326-6066.CIR-24-0384","DOIUrl":"10.1158/2326-6066.CIR-24-0384","url":null,"abstract":"<p><p>Many tumor-specific monoclonal antibody therapies stimulate antibody-dependent cellular cytotoxicity (ADCC) by natural killer (NK) cells through FcγRIIIa (CD16). The efficacy of these ADCC-based immunotherapies is potentiated in patients with the common CD16 polymorphic variant F158-V that increases the binding affinity between the receptor and the IgG Fc domain. However, other CD16 variants are less well characterized. Here, we report that CD16 L48-H and L48-R variants both significantly enhance in vitro ADCC responses in primary NK cells and NK-92 cells. During ADCC responses, NK cells expressing CD16 48-H killed and disengaged from target cells faster than those expressing CD16 48-L, resulting in improved serial killing of tumor cells. We found that CD16 48-H also formed an immunologic synapse with a more compact interface, as well as more robust intracellular calcium signaling and quicker polarization of cytolytic vesicles. The ADCC response observed occurs due to increased cytolytic signaling and target cell disengagement, which drives NK cell-mediated serial killing of tumor cells. The L48-H/R polymorphism has potential to benefit patient responses to cancer antibody therapies and may also potentiate antitumor ADCC responses if incorporated into adoptive NK cell therapeutic platforms.</p>","PeriodicalId":9474,"journal":{"name":"Cancer immunology research","volume":" ","pages":"417-429"},"PeriodicalIF":8.2,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11879761/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142811753","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":"The HSP90 Inhibitor Pimitespib Targets Regulatory T Cells in the Tumor Microenvironment.","authors":"Ayaka Tsuge, Sho Watanabe, Akihito Kawazoe, Yosuke Togashi, Kota Itahashi, Mari Masuda, Atsuo Sai, Shogo Takei, Hiromi Muraoka, Shuichi Ohkubo, Daisuke Sugiyama, Yue Yan, Shota Fukuoka, Toshihiko Doi, Kohei Shitara, Shohei Koyama, Hiroyoshi Nishikawa","doi":"10.1158/2326-6066.CIR-24-0713","DOIUrl":"10.1158/2326-6066.CIR-24-0713","url":null,"abstract":"<p><p>Regulatory T (Treg) cells play key roles in cancer immunity by suppressing a range of antitumor immune responses and contributing to resistance to PD-1 blockade therapy. Given their critical roles in self-tolerance, local control of immunosuppression by Treg cells, such as in the tumor microenvironment, has been intensively studied. Inhibition of HSP90, a chaperone with vital roles in regulating proteostasis in cancer cells, impedes cancer progression by interrupting oncogenic signaling pathways and potentially modulating antitumor immunity, but we have very little mechanistic insight into these immune modulatory effects. In this study, we show that the number of Treg cells is selectively reduced by the HSP90 inhibitor pimitespib in animal models and patients with gastric cancer in a clinical trial (EPOC1704). Pimitespib reduced the highly immunosuppressive human FOXP3high effector Treg cells by inhibiting their proliferation and decreasing their expression of effector molecules, which improved the priming and activation of antigen-specific CD8+ T cells. Mechanistic studies revealed that pimitespib selectively degraded STAT5, a key transducer of the IL2 signaling pathway, which is essential for Treg cell development and maintenance, and consequently compromised FOXP3 expression, leading to selective impairment of immunosuppression in the tumor microenvironment by Treg cells. Thus, pimitespib treatment combined with PD-1 blockade exhibited a far stronger antitumor effect than either treatment alone in animal models. Through these data, we propose that HSP90 inhibition is a promising therapeutic option for Treg cell-targeted cancer immunotherapy.</p>","PeriodicalId":9474,"journal":{"name":"Cancer immunology research","volume":" ","pages":"273-285"},"PeriodicalIF":8.1,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142738522","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":"Identification and Phenotypic Characterization of Neoantigen-Specific Cytotoxic CD4+ T Cells in Endometrial Cancer.","authors":"Minami Fusagawa, Serina Tokita, Kenji Murata, Tasuku Mariya, Mina Umemoto, Shintaro Sugita, Kazuhiko Matsuo, Yoshihiko Hirohashi, Tsuyoshi Saito, Takayuki Kanaseki, Toshihiko Torigoe","doi":"10.1158/2326-6066.CIR-24-0514","DOIUrl":"10.1158/2326-6066.CIR-24-0514","url":null,"abstract":"<p><p>Tumor-reactive CD4+ T cells often accumulate in the tumor microenvironment (TME) in human cancer, but their functions and roles in antitumor responses remain elusive. Here, we investigated the immunopeptidome of HLA class II-positive (HLA-II+) endometrial cancer with an inflamed TME using a proteogenomic approach. We identified HLA-II neoantigens, one of which induced polyclonal CD4+ tumor-infiltrating lymphocyte responses. We then experimentally demonstrated that neoantigen-specific CD4+ tumor-infiltrating lymphocytes lyse target cells in an HLA-II-dependent manner. Single-cell transcriptomic analysis of the TME coupled with T-cell receptor sequencing revealed the presence of CD4+ T-cell clusters characterized by CXCL13 expression. The CXCL13+ clusters contained two subclusters with distinct cytotoxic gene expression patterns. The identified neoantigen-specific CD4+ T cells were found exclusively in one of the CXCL13+ subclusters characterized by granzyme B and CCL5 expression. These results demonstrate the involvement of tumor-reactive CD4+ T cells with cytotoxic function in immune surveillance of endometrial cancer and reveal their transcriptomic signature.</p>","PeriodicalId":9474,"journal":{"name":"Cancer immunology research","volume":" ","pages":"171-184"},"PeriodicalIF":8.1,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142799403","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":"Hyperthermic Intrathoracic Chemotherapy Modulates the Immune Microenvironment of Pleural Mesothelioma and Improves the Impact of Dual Immune Checkpoint Inhibition.","authors":"Yameng Hao, Aspasia Gkasti, Amy J Managh, Julien Dagher, Alexandros Sifis, Luca Tiron, Louis-Emmanuel Chriqui, Damien N Marie, Olga De Souza Silva, Michel Christodoulou, Solange Peters, Johanna A Joyce, Thorsten Krueger, Michel Gonzalez, Etienne Abdelnour-Berchtold, Christine Sempoux, Daniel Clerc, Hugo Teixeira-Farinha, Martin Hübner, Etienne Meylan, Paul J Dyson, Sabrina Cavin, Jean Y Perentes","doi":"10.1158/2326-6066.CIR-24-0245","DOIUrl":"10.1158/2326-6066.CIR-24-0245","url":null,"abstract":"<p><p>Pleural mesothelioma is a fatal disease with limited treatment options. Recently, pleural mesothelioma management has improved with the development of immune checkpoint inhibitors (ICI). In first-line therapy, dual PD-1 and CTLA-4 blockade enhances tumor control and patient survival compared with chemotherapy. Unfortunately, only a fraction of patients is responsive to immunotherapy, and approaches to reshape the tumor immune microenvironment and make ICIs more effective are urgently required. In this study, we evaluated the effect of hyperthermic intrathoracic chemotherapy (HITOC), a treatment that combines fever-range hyperthermia with local intrapleural cisplatin chemotherapy, on the tumor immune microenvironment and response to ICIs. To do this, we developed a murine pleural mesothelioma model of HITOC. We found that HITOC significantly improved tumor control and animal survival through a mechanism involving the development of a cytotoxic immune response. Additionally, HITOC enhanced immune checkpoint expression by T lymphocytes and synergized with dual PD-1 and CTLA-4 inhibition, leading to further improvement in animal survival. Finally, the analysis of peritoneal mesothelioma patient samples treated by pressurized intraperitoneal aerosol chemotherapy revealed a similar immunomodulation. In conclusion, HITOC remodels the tumor immune microenvironment of pleural mesothelioma by promoting T-cell infiltration into the tumor and could be considered in combination with ICIs in the context of a clinical trial.</p>","PeriodicalId":9474,"journal":{"name":"Cancer immunology research","volume":" ","pages":"185-199"},"PeriodicalIF":8.1,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142709128","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":"Targeting of Tumoral NAC1 Mitigates Myeloid-Derived Suppressor Cell-Mediated Immunosuppression and Potentiates Anti-PD-1 Therapy in Ovarian Cancer.","authors":"Shunli Dong, Cong Ye, Bin Li, Fanglin Lv, Lu Zhang, Shumin Yang, Fang Wang, Mingxian Zhu, Mingxuan Zhou, Fanfan Guo, Zhenyun Li, Lei Peng, Cheng Ji, Xialiang Lu, Yan Cheng, Xingcong Ren, Youguo Chen, Jinhua Zhou, Jinming Yang, Yi Zhang","doi":"10.1158/2326-6066.CIR-24-0084","DOIUrl":"10.1158/2326-6066.CIR-24-0084","url":null,"abstract":"<p><p>Epithelial ovarian cancer is the most common type of ovarian cancer with a low rate of response to immunotherapy such as immune checkpoint blockade therapy. In this study, we report that nucleus accumbens-associated protein 1 (NAC1), a putative driver of epithelial ovarian cancer, has a critical role in immune evasion. We showed in murine ovarian cancer models that depleting or inhibiting tumoral NAC1 reduced the recruitment and immunosuppressive function of myeloid-derived suppressor cells (MDSC) in the tumor microenvironment, led to significant increases of cytotoxic tumor-infiltrating CD8+ T cells, and promoted antitumor immunity and suppressed tumor progression. We further showed that tumoral NAC1 directly enhanced the transcription of CXCL16 by binding to CXCR6, thereby promoting MDSC recruitment to the tumor. Moreover, lipid C20:1T produced by NAC1-expressing tumor cells fueled oxidative metabolism of MDSCs and promoted their immune-suppressive function. We also showed that NIC3, a small-molecule inhibitor of NAC1, was able to sensitize mice bearing NAC1-expressing ovarian tumors to anti-PD-1 therapy. Our study reveals a critical role for NAC1 in controlling tumor infiltration of MDSCs and in modulating the efficacy of immune checkpoint blockade therapy. Thus, targeting of NAC1 may be exploited to sensitize ovarian cancer to immunotherapy.</p>","PeriodicalId":9474,"journal":{"name":"Cancer immunology research","volume":" ","pages":"286-302"},"PeriodicalIF":8.1,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142614540","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":"Inflammatory Stress Determines the Need for Chemotherapy in Patients with HER2-Positive Esophagogastric Adenocarcinoma Receiving Targeted Therapy and Immunotherapy.","authors":"Joseph Tintelnot, Lisa Paschold, Eray Goekkurt, Christoph Schultheiss, Urte Matschl, Mariana Santos Cruz, Marcus Bauer, Claudia Wickenhauser, Peter Thuss-Patience, Sylvie Lorenzen, Thomas J Ettrich, Jorge Riera-Knorrenschild, Lutz Jacobasch, Albrecht Kretzschmar, Stefan Kubicka, Salah-Eddin Al-Batran, Anke Reinacher-Schick, Daniel Pink, Carsten Bokemeyer, Marianne Sinn, Udo Lindig, Axel Hinke, Susanna Hegewisch-Becker, Alexander Stein, Mascha Binder","doi":"10.1158/2326-6066.CIR-24-0561","DOIUrl":"10.1158/2326-6066.CIR-24-0561","url":null,"abstract":"<p><p>Anti-PD-1, trastuzumab, and chemotherapy are used in the treatment of patients with advanced HER2-positive esophagogastric adenocarcinoma, but long-term survival remains limited. In this study, we report extended follow-up data from the INTEGA trial (NCT03409848), which investigated the efficacy of the anti-PD-1 nivolumab, trastuzumab, and FOLFOX chemotherapy (FOLFOX arm) in comparison with a chemotherapy-free regimen involving nivolumab, trastuzumab, and the anti-CTLA-4 ipilimumab (Ipi arm) in the first-line setting for advanced disease. The 12-month overall survival (OS) showed no statistical difference between the arms, with 57% OS (95% confidence interval, 41%-71%) in the Ipi arm and 70% OS (95% confidence interval, 54%-82%) in the FOLFOX arm. Crossing of the survival curves indicated a potential long-term benefit for some patients within the Ipi arm, but early progressors in the Ipi arm underlined the need for biomarker-guided strategies to optimize treatment selection. To this end, metabolomic and cytokine analyses demonstrated elevated levels of normetanephrine, cortisol, and IL6 in immunotherapy-unresponsive patients in the Ipi arm, suggesting a role for systemic inflammatory stress in modulating antitumor immune responses. Patients with this signature also showed an increased neutrophil to lymphocyte ratio that persisted in the Ipi arm, but not in the FOLFOX arm, and strongly correlated with survival. Furthermore, a low neutrophil to lymphocyte ratio characterized patients benefiting from immunotherapy and targeted therapy without the need for additional chemotherapy. These data suggest that patient selection based on inflammatory stress-driven immune changes could help customize first-line treatment in patients with advanced HER2-positive esophagogastric adenocarcinoma to potentially improve long-term survival.</p>","PeriodicalId":9474,"journal":{"name":"Cancer immunology research","volume":" ","pages":"200-209"},"PeriodicalIF":8.1,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11788649/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142614424","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-13-2-WWR","DOIUrl":"https://doi.org/10.1158/2326-6066.CIR-13-2-WWR","url":null,"abstract":"","PeriodicalId":9474,"journal":{"name":"Cancer immunology research","volume":"13 2","pages":"161"},"PeriodicalIF":8.1,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143078750","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}