Cancer Immunology, Immunotherapy最新文献

{"title":"Tumor immunogenicity regulates host immune responses, and conventional dendritic cell type 2 uptakes the majority of tumor antigens in an orthotopic lung cancer model.","authors":"Ki-Hyun Kim, Seung-Jae Kim, Jacob D Eccles, Christian Ascoli, Gye Young Park","doi":"10.1007/s00262-024-03828-w","DOIUrl":"10.1007/s00262-024-03828-w","url":null,"abstract":"<p><p>Human lung cancer carries high genetic alterations, expressing high tumor-specific neoantigens. Although orthotopic murine lung cancer models recapitulate many characteristics of human lung cancers, genetically engineered mouse models have fewer somatic mutations than human lung cancer, resulting in scarce immune cell infiltration and deficient immune responses. The endogenous mouse lung cancer model driven by Kras mutation and Trp53 deletion (KP model) has minimal immune infiltration because of a scarcity of neoantigens. Fine-tuning tumor antigenicity to trigger the appropriate level of antitumor immunity would be key to investigating immune responses against human lung cancer. We engineered the KP model to express antigens of OVA peptides (minOVA) as neoantigens along with ZsGreen, a traceable fluorescent conjugate. The KP model expressing minOVA exhibited stronger immunogenicity with higher immune cell infiltration comprised of CD8⁺ T cells and CD11c⁺ dendritic cells (DCs). Consequently, the KP model expressing minOVA exhibits suppressed tumor growth compared to its origin. We further analyzed tumor-infiltrated DCs. The majority of ZsGreen conjugated with minOVA was observed in the conventional type 2 DCs (cDC2), whereas cDC1 has minimal. These data indicate that tumor immunogenicity regulates host immune responses, and tumor neoantigen is mostly recognized by cDC2 cells, which may play a critical role in initiating antitumor immune responses in an orthotopic murine lung cancer model.</p>","PeriodicalId":9595,"journal":{"name":"Cancer Immunology, Immunotherapy","volume":"73 12","pages":"237"},"PeriodicalIF":5.4,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11447165/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142364528","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":"Efficacy and safety of lenvatinib combined with anti-PD-1 antibodies plus GEMOX chemotherapy as non-first-line systemic therapy in advanced gallbladder cancer.","authors":"Yang Tan, Kai Liu, Chengpei Zhu, Shanshan Wang, Yunchao Wang, Jingnan Xue, Cong Ning, Nan Zhang, Jiashuo Chao, Longhao Zhang, Junyu Long, Xiaobo Yang, Daobing Zeng, Lijin Zhao, Haitao Zhao","doi":"10.1007/s00262-024-03831-1","DOIUrl":"10.1007/s00262-024-03831-1","url":null,"abstract":"<p><strong>Background: </strong>Lenvatinib, programmed cell death 1 (PD-1) antibodies, and gemcitabine and oxaliplatin (GEMOX) chemotherapy have shown significant antitumor activity as first-line therapy against biliary tract cancer. This study evaluated their efficacy and safety as non-first-line therapy in advanced gallbladder cancer (GBC).</p><p><strong>Methods: </strong>Patients with advanced GBC who received lenvatinib combined with anti-PD-1 antibodies and GEMOX chemotherapy as a non-first-line therapy were retrospectively analyzed. The primary endpoints were overall survival (OS) and progression-free survival (PFS), and the secondary endpoints were objective response rate (ORR) and safety.</p><p><strong>Results: </strong>A total of 36 patients with advanced GBC were included in this study. The median follow-up time was 11.53 (95% confidence interval (CI): 2.2-20.9) months, and the ORR was 36.1%. The median OS and PFS were 15.1 (95% CI: 3.2-26.9) and 6.1 (95% CI: 4.9-7.2) months, respectively. The disease control rate (DCR) and clinical benefit rate (CBR) were 75% and 61.1%, respectively. Subgroup analysis demonstrated that patients with programmed cell death-ligand 1 (PD-L1) expression had significantly longer PFS and OS than those without PD-L1 expression. Additionally, patients with a neutrophil-lymphocyte ratio (NLR) < 5.57 had a longer OS than those with an NLR ≥ 5.57. All patients experienced adverse events (AEs), with 61.1% experiencing grade 3 or 4 AEs, including myelosuppression (13.9%) and fatigue (13.3%), alanine transaminase or aspartate transaminase levels (8.3%), and diarrhea (8.3%). No grade 5 AEs were reported.</p><p><strong>Conclusion: </strong>Anti-PD-1 antibodies combined with lenvatinib and GEMOX chemotherapy are effective and well-tolerated as a non-first-line therapy in advanced GBC. PD-L1 expression and baseline NLR may potentially predict treatment efficacy.</p>","PeriodicalId":9595,"journal":{"name":"Cancer Immunology, Immunotherapy","volume":"73 12","pages":"240"},"PeriodicalIF":4.6,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11447189/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142364447","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":"NitraTh epitope-based neoantigen vaccines for effective tumor immunotherapy.","authors":"Wanli Zhang, Xupeiyao Shi, Shitong Huang, Qiumin Yu, Zijie Wu, Wenbin Xie, Binghua Li, Yanchao Xu, Zheng Gao, Guozhi Li, Qianqian Qian, Tiandi He, Jiaxue Zheng, Tingran Zhang, Yue Tong, Danni Deng, Xiangdong Gao, Hong Tian, Wenbing Yao","doi":"10.1007/s00262-024-03830-2","DOIUrl":"10.1007/s00262-024-03830-2","url":null,"abstract":"<p><p>Neoantigen vaccines represent an emerging and promising strategy in the field of tumor immunotherapy. Despite their potential, designing an effective neoantigen vaccine remains a challenge due to the current limitations in predicting CD4⁺ T cell epitopes with high accuracy. Here, we introduce a novel approach to neoantigen vaccine design that does not rely on computational prediction of CD4⁺ T cell epitopes. Utilizing nitrated helper T cell epitope containing p-nitrophenylalanine, termed \"NitraTh epitope,\" we have successfully engineered a series of tumor neoantigen vaccines capable of eliciting robust neoantigen-specific immune responses. With the help of NitraTh epitope, even mutations with low predicted affinity for MHC class I molecules were successfully induced to elicit neoantigen-specific responses. In H22 cell allograft and patient-derived xenograft (PDX) liver cancer mouse models, the NitraTh epitope-based neoantigen vaccines significantly suppressed tumor progression. More strikingly, through single-cell sequencing we found that the NitraTh epitope-based neoantigen vaccines regulate macrophage reprogramming and modulate macrophages to decrease the levels of the immunosuppressive molecule prostaglandin E2 (PGE2), which in turn reshapes the tumor immunosuppressive microenvironment. In summary, NitraTh epitope-based neoantigen vaccines possess the dual effects of potently activating neoantigen-specific immunity and alleviating immunosuppression, potentially providing a new paradigm for the design of tumor neoantigen vaccines.</p>","PeriodicalId":9595,"journal":{"name":"Cancer Immunology, Immunotherapy","volume":"73 12","pages":"245"},"PeriodicalIF":5.4,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11447171/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142364522","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":"The relevance of tumor target expression levels on IgA-mediated cytotoxicity in cancer immunotherapy.","authors":"Chilam Chan, Núria Casalé Cabanes, J H Marco Jansen, Joël Guillaume, Maaike Nederend, Elsemieke M Passchier, Valentina E Gómez-Mellado, Matthias Peipp, Marianne Boes, Geert van Tetering, Jeanette H W Leusen","doi":"10.1007/s00262-024-03824-0","DOIUrl":"10.1007/s00262-024-03824-0","url":null,"abstract":"<p><p>Recent advances in cancer immunotherapy, particularly the success of immune checkpoint inhibitors, have reignited interest in targeted monoclonal antibodies for immunotherapy. Antibody therapies aim to minimize on-target, off-tumor toxicity by targeting antigens overexpressed on tumor cells but not on healthy cells. Despite considerable efforts, some therapeutic antibodies have been linked to dose-limiting side effects. Our hypothesis suggests that the efficacy of IgG leads to a lower target expression threshold for tumor cell killing, contributing to these side effects. Earlier, therapeutic IgG antibodies were reformatted into the IgA isotype. Unlike IgG, which primarily engages Fc gamma receptors (FcγR) to induce antibody-dependent cellular cytotoxicity (ADCC) by NK cells and antibody-dependent cellular phagocytosis (ADCP) by monocytes/macrophages, IgA antibodies activate neutrophils through the Fc alpha receptor I (CD89, FcαRI). In previous studies, it appeared that IgA may require a higher target expression threshold for effective killing, and we aimed to investigate this in our current study. Moreover, we investigated how blocking the myeloid checkpoint CD47/SIRPα axis affect the target expression threshold. Using a tetracycline-inducible expression system, we regulated target expression in different cell lines. Our findings from ADCC assays indicate that IgA-mediated PMN ADCC requires a higher antigen expression level than IgG-mediated PBMC ADCC. Furthermore, blocking CD47 enhanced IgA-mediated ADCC, lowering the antigen threshold. Validated in two in vivo models, our results show that IgA significantly reduces tumor growth in high-antigen-expressing tumors without affecting low-antigen-expressing healthy tissues. This suggests IgA-based immunotherapy could potentially minimize on-target, off-tumor side effects, improving treatment efficacy and patient safety.</p>","PeriodicalId":9595,"journal":{"name":"Cancer Immunology, Immunotherapy","volume":"73 12","pages":"238"},"PeriodicalIF":5.4,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11447191/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142364525","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":"Development and validation of a new tool to estimate early mortality in patients with advanced cancer treated with immunotherapy.","authors":"Andrea De Giglio, Alessandro Leonetti, Francesca Comito, Daria Maria Filippini, Veronica Mollica, Karim Rihawi, Marianna Peroni, Giulia Mazzaschi, Ilaria Ricciotti, Francesca Carosi, Andrea Marchetti, Matteo Rosellini, Ambrogio Gagliano, Valentina Favorito, Elisabetta Nobili, Francesco Gelsomino, Barbara Melotti, Paola Valeria Marchese, Francesca Sperandi, Alessandro Di Federico, Sebastiano Buti, Fabiana Perrone, Francesco Massari, Maria Abbondanza Pantaleo, Marcello Tiseo, Andrea Ardizzoni","doi":"10.1007/s00262-024-03836-w","DOIUrl":"10.1007/s00262-024-03836-w","url":null,"abstract":"<p><strong>Background: </strong>Immune checkpoint inhibitors (ICIs) are standard treatments for advanced solid cancers. Resistance to ICIs, both primary and secondary, poses challenges, with early mortality (EM) within 30-90 days indicating a lack of benefit. Prognostic factors for EM, including the lung immune prognostic index (LIPI), remain underexplored.</p><p><strong>Methods: </strong>We performed a retrospective, observational study including patients affected by advanced solid tumors, treated with ICI as single agent or combined with other agents. Logistic regression models identified factors associated with EM and 90-day progression risks. A nomogram for predicting 90-day mortality was built and validated within an external cohort.</p><p><strong>Results: </strong>In total, 637 patients received ICIs (single agent or in combination with other drugs) for advanced solid tumors. Most patients were male (61.9%), with NSCLC as the prevalent tumor (61.8%). Within the cohort, 21.3% died within 90 days, 8.4% died within 30 days, and 34.5% experienced early progression. Factors independently associated with 90-day mortality included ECOG PS 2 and a high/intermediate LIPI score. For 30-day mortality, lung metastasis and a high/intermediate LIPI score were independent risk factors. Regarding early progression, high/intermediate LIPI score was independently associated. A predictive nomogram for 90-day mortality combining LIPI and ECOG PS achieved an AUC of 0.76 (95% CI 0.71-0.81). The discrimination ability of the nomogram was confirmed in the external validation cohort (n = 255) (AUC 0.72, 95% CI 0.64-0.80).</p><p><strong>Conclusion: </strong>LIPI and ECOG PS independently were able to estimate 90-day mortality, with LIPI also demonstrating prognostic validity for 30-day mortality and early progression.</p>","PeriodicalId":9595,"journal":{"name":"Cancer Immunology, Immunotherapy","volume":"73 12","pages":"246"},"PeriodicalIF":5.4,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11447166/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142364520","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":"A random survival forest-based pathomics signature classifies immunotherapy prognosis and profiles TIME and genomics in ES-SCLC patients.","authors":"Yuxin Jiang, Yueying Chen, Qinpei Cheng, Wanjun Lu, Yu Li, Xueying Zuo, Qiuxia Wu, Xiaoxia Wang, Fang Zhang, Dong Wang, Qin Wang, Tangfeng Lv, Yong Song, Ping Zhan","doi":"10.1007/s00262-024-03829-9","DOIUrl":"10.1007/s00262-024-03829-9","url":null,"abstract":"<p><strong>Background: </strong>Small cell lung cancer (SCLC) is a highly aggressive neuroendocrine tumor with high mortality, and only a limited subset of extensive-stage SCLC (ES-SCLC) patients demonstrate prolonged survival under chemoimmunotherapy, which warrants the exploration of reliable biomarkers. Herein, we built a machine learning-based model using pathomics features extracted from hematoxylin and eosin (H&E)-stained images to classify prognosis and explore its potential association with genomics and TIME.</p><p><strong>Methods: </strong>We retrospectively recruited ES-SCLC patients receiving first-line chemoimmunotherapy at Nanjing Jinling Hospital between April 2020 and August 2023. Digital H&E-stained whole-slide images were acquired, and targeted next-generation sequencing, programmed death ligand-1 staining, and multiplex immunohistochemical staining for immune cells were performed on a subset of patients. A random survival forest (RSF) model encompassing clinical and pathomics features was established to predict overall survival. The function of putative genes was assessed via single-cell RNA sequencing.</p><p><strong>Results and conclusion: </strong>During the median follow-up period of 12.12 months, 118 ES-SCLC patients receiving first-line immunotherapy were recruited. The RSF model utilizing three pathomics features and liver metastases, bone metastases, smoking status, and lactate dehydrogenase, could predict the survival of first-line chemoimmunotherapy in patients with ES-SCLC with favorable discrimination and calibration. Underlyingly, the higher RSF-Score potentially indicated more infiltration of CD8⁺ T cells in the stroma as well as a greater probability of MCL-1 amplification and EP300 mutation. At the single-cell level, MCL-1 was associated with TNFA-NFKB signaling and apoptosis-related processes. Hopefully, this noninvasive model could act as a biomarker for immunotherapy, potentially facilitating precision medicine in the management of ES-SCLC.</p>","PeriodicalId":9595,"journal":{"name":"Cancer Immunology, Immunotherapy","volume":"73 12","pages":"241"},"PeriodicalIF":5.4,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11448477/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142364519","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":"PD-1 blockade does not improve efficacy of EpCAM-directed CAR T-cell in lung cancer brain metastasis.","authors":"Jens Blobner, Laura Dengler, Constantin Eberle, Julika J Herold, Tao Xu, Alexander Beck, Anton Mühlbauer, Katharina J Müller, Nico Teske, Philipp Karschnia, Dominic van den Heuvel, Ferdinand Schallerer, Hellen Ishikawa-Ankerhold, Niklas Thon, Joerg-Christian Tonn, Marion Subklewe, Sebastian Kobold, Patrick N Harter, Veit R Buchholz, Louisa von Baumgarten","doi":"10.1007/s00262-024-03837-9","DOIUrl":"10.1007/s00262-024-03837-9","url":null,"abstract":"<p><strong>Background: </strong>Lung cancer brain metastasis has a devastating prognosis, necessitating innovative treatment strategies. While chimeric antigen receptor (CAR) T-cell show promise in hematologic malignancies, their efficacy in solid tumors, including brain metastasis, is limited by the immunosuppressive tumor environment. The PD-L1/PD-1 pathway inhibits CAR T-cell activity in the tumor microenvironment, presenting a potential target to enhance therapeutic efficacy. This study aims to evaluate the impact of anti-PD-1 antibodies on CAR T-cell in treating lung cancer brain metastasis.</p><p><strong>Methods: </strong>We utilized a murine immunocompetent, syngeneic orthotopic cerebral metastasis model for repetitive intracerebral two-photon laser scanning microscopy, enabling in vivo characterization of red fluorescent tumor cells and CAR T-cell at a single-cell level over time. Red fluorescent EpCAM-transduced Lewis lung carcinoma cells (^EpCAM/tdtLL/2 cells) were implanted intracranially. Following the formation of brain metastasis, EpCAM-directed CAR T-cell were injected into adjacent brain tissue, and animals received either anti-PD-1 or an isotype control.</p><p><strong>Results: </strong>Compared to controls receiving T-cell lacking a CAR, mice receiving EpCAM-directed CAR T-cell showed higher intratumoral CAR T-cell densities in the beginning after intraparenchymal injection. This finding was accompanied with reduced tumor growth and translated into a survival benefit. Additional anti-PD-1 treatment, however, did not affect intratumoral CAR T-cell persistence nor tumor growth and thereby did not provide an additional therapeutic effect.</p><p><strong>Conclusion: </strong>CAR T-cell therapy for brain malignancies appears promising. However, additional anti-PD-1 treatment did not enhance intratumoral CAR T-cell persistence or effector function, highlighting the need for novel strategies to improve CAR T-cell therapy in solid tumors.</p>","PeriodicalId":9595,"journal":{"name":"Cancer Immunology, Immunotherapy","volume":"73 12","pages":"255"},"PeriodicalIF":5.4,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11447167/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142364523","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":"Toripalimab combined with definitive chemoradiotherapy for locally advanced cervical squamous cell carcinoma patients (TRACE): A single-arm, phase I/II trial.","authors":"Dan Ou, Rong Cai, Wei-Xiang Qi, Can Cui, Lu Cao, Shu-Bei Wang, Huan Li, Tao Ma, Ying Miao, Cheng Xu, Gang Cai, Wei-Guo Cao, Yun-Sheng Gao, Jia-Yi Chen, Hao-Ping Xu","doi":"10.1007/s00262-024-03823-1","DOIUrl":"10.1007/s00262-024-03823-1","url":null,"abstract":"<p><strong>Purpose: </strong>This phase I/II trial (ChiCTR2000032879) assessed the safety and efficacy of toripalimab combined with chemoradiotherapy for locally advanced cervical squamous cell carcinoma.</p><p><strong>Methods and materials: </strong>Twenty-two patients, regardless of their programmed death ligand-1 (PD-L1) status, received toripalimab combined with concurrent chemoradiotherapy (CCRT). CCRT included cisplatin (40 mg/m², once weekly for 5 weeks), radiotherapy (45-50.4 Gy/25-28 Fx, 5 fractions weekly), followed by brachytherapy (24-30 Gy/3-5 Fx) and toripalimab (240 mg, intravenous) on days 1, 22 and 43 during CCRT. The primary endpoints were safety and 2-year progression-free survival (PFS). The secondary endpoints included 2-year local control (LC), local regional control and overall survival (OS).</p><p><strong>Results: </strong>All patients successfully completed CCRT and toripalimab treatment. Grade III and higher adverse events (AEs) were observed in 11 patients (11/22, 50%), and no patient experienced grade V AEs. The objective response rate (ORR) was 100%. At the data cutoff (June 30, 2023), the median follow-up was 31.8 months (9.5 to 37.8 months). The 2-year PFS rate was 81.8%. The 2-year LC and local regional control rates were both 95.5%, and the 2-year OS rate was 90.9%.</p><p><strong>Conclusions: </strong>Toripalimab combined with CCRT achieved good tolerance and showed promising anti-tumor effects in patients with locally advanced cervical cancer.</p>","PeriodicalId":9595,"journal":{"name":"Cancer Immunology, Immunotherapy","volume":"73 12","pages":"244"},"PeriodicalIF":5.4,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11447187/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142364527","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":"Effectiveness, safety, and biomarker analysis of lenvatinib plus toripalimab as chemo-free therapy in advanced intrahepatic cholangiocarcinoma: a real-world study.","authors":"Shanshan Wang, Jiashuo Chao, Hao Wang, Shuofeng Li, Yunchao Wang, Chengpei Zhu, Nan Zhang, Mingjian Piao, Xu Yang, Kai Liu, Ziyu Xun, Xinting Sang, Xiaobo Yang, Weidong Duan, Haitao Zhao","doi":"10.1007/s00262-024-03841-z","DOIUrl":"10.1007/s00262-024-03841-z","url":null,"abstract":"<p><strong>Background: </strong>Treatment options for advanced intrahepatic cholangiocarcinoma (ICC) are currently limited. Chemo-containing regimens are the mainstay treatments but associated with notable toxicity, poor tolerance, and reduced compliance, necessitating exploration of alternative therapies. Lenvatinib plus PD-1 inhibitors has shown substantial clinical activity in preliminary studies. This study aimed to assess the effectiveness and safety of lenvatinib plus toripalimab (a novel PD-1 antibody) as chemo-free therapy in advanced ICC.</p><p><strong>Methods: </strong>This retrospective study included consecutive advanced ICC patients receiving lenvatinib plus toripalimab between February 2019 and December 2023. The main outcomes were overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and safety. Prognostic factors and exploratory analyses for genetic alternations were also conducted.</p><p><strong>Results: </strong>A total of 78 patients were included, with a median follow-up of 25.9 months. Median OS and PFS were 11.3 (95% CI: 9.5-13.1) and 5.4 (95% CI: 3.8-7.0) months, respectively. ORR was 19.2% and DCR was 75.6%. The incidence of grade 3 or 4 adverse events (AEs) was 50.0%, with no grade 5 AEs reported. Patients with normal baseline CA19-9 levels exhibited a higher ORR (p = 0.011), longer PFS (11.5 versus 4.6 months; HR 0.47; p=0.005), and OS (21.0 versus 9.7 months; HR 0.43; p=0.003). The presence of IDH1 mutations correlated with increased ORR (60.0% versus 8.9%, p=0.016).</p><p><strong>Conclusion: </strong>Lenvatinib plus toripalimab represents an effective and well-tolerated chemo-free therapeutic option for advanced ICC. Baseline CA19-9 levels and IDH1 mutations may serve as predictive treatment-related biomarkers.</p>","PeriodicalId":9595,"journal":{"name":"Cancer Immunology, Immunotherapy","volume":"73 12","pages":"249"},"PeriodicalIF":5.4,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11447168/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142364446","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":"GPCRs: emerging targets for novel T cell immune checkpoint therapy.","authors":"Kaitlyn Dickinson, Elliott J Yee, Isaac Vigil, Richard D Schulick, Yuwen Zhu","doi":"10.1007/s00262-024-03801-7","DOIUrl":"10.1007/s00262-024-03801-7","url":null,"abstract":"<p><p>Although immune checkpoint blockade (ICB) has become the mainstay of treatment for advanced solid organ malignancies, success in revitalizing the host anticancer immune response remains limited. G-protein coupled receptors (GPCRs) are a broad family of cell-surface proteins that have been regarded as main players in regulating the immune system, namely by mediating the activity of T lymphocytes. Among the most novel immunoregulatory GPCRs include GPR171, lysophosphatidic acid receptors (LPARs), GPR68, cannabinoid receptor 2 (CB2), and prostaglandin E receptors, many of which have shown promise in mediating antitumor response via activation of cytotoxic T cells, inhibiting immunosuppressive lymphocytes, and facilitating immune cell infiltration within the tumor microenvironment across multiple types of cancers. This paper reviews our current understanding of some of the most novel GPCRs-their expression patterns, evolving roles within the immune system and cancer, potential therapeutic applications, and perspective for future investigation.</p>","PeriodicalId":9595,"journal":{"name":"Cancer Immunology, Immunotherapy","volume":"73 12","pages":"253"},"PeriodicalIF":5.4,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11447192/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142364450","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}