Cancer Immunology, Immunotherapy最新文献

{"title":"CMV IgG in the blood is not associated with hepatitis but correlates with poor outcomes in immunotherapy treated melanoma patients.","authors":"Sophia B Strobel, Devayani Machiraju, Melanie Wiecken, Jasmin Richter, Julian A F Klein, Annemarie Berger, Jessica C Hassel","doi":"10.1007/s00262-024-03859-3","DOIUrl":"10.1007/s00262-024-03859-3","url":null,"abstract":"<p><p>Cytomegalovirus (CMV) infection or reactivation in immune-compromised individuals can lead to a wide range of severe complications including hepatitis. However, its relation with immune checkpoint inhibitors (ICIs) induced hepatitis (ICI-hepatitis) and tumor responses in advanced melanoma patients remains unclear. Hundred and ninety metastatic cutaneous melanoma patients (mCM) who received ICI treatment, with CMV IgG or IgM information available at baseline, were included in the study (Cohort 1). Clinical characteristics and immune cell count in the blood were retrieved from medical records. In addition, anti-CMV IgG and IgM were measured in pre and on-treatment serum samples from 49 advanced skin cancer patients using ELISA (Cohort 2). In the event of a positive anti-CMV IgM, further analysis with PCR was performed. Univariate and multivariate analysis was used to assess the relationship between CMV IgG or IgM and ICI-hepatitis tumor outcomes. Twenty-one patients (11%) developed hepatitis during ICI treatment (Cohort 1). ICI-hepatitis was significantly associated with disease control rate (DCR; p = 0.017) and longer progression-free survival (PFS; p = 0.008) in mCM patients. Detection of CMV IgG or IgM antibodies were not associated with ICI-hepatitis (p > 0.05). However, increased CMV IgG values at baseline correlated with disease progression (p = 0.047) and shorter PFS (p = 0.081). In addition, increased CMV IgG values were associated with reduced levels of monocytes (p = 0.005), eosinophils (p = 0.062), and neutrophils (p = 0.065) in the blood. In summary, anti-CMV IgG or IgM in the blood may not be associated with ICI-hepatitis, but high anti-CMV IgG at baseline indicates poor outcomes in ICI-treated mCM patients.</p>","PeriodicalId":9595,"journal":{"name":"Cancer Immunology, Immunotherapy","volume":"74 2","pages":"59"},"PeriodicalIF":4.6,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11699187/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142919595","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":"FcRn-guided antigen trafficking enhances cancer vaccine efficacy.","authors":"Mengyu Hong, Muziying Liu, Fang Zhu, Dan Zhao, Guilai Liu, Tiyun Han, Caiyi Fei, Weihong Zeng, Shi Chen, Qiqin Wu, Bofeng Li, Songquan Wu, Yuhua Shang, Huan Ma, Shoubing Zhou, Shi Xu, Tengchuan Jin","doi":"10.1007/s00262-024-03888-y","DOIUrl":"10.1007/s00262-024-03888-y","url":null,"abstract":"<p><p>The development of tumor vaccines represents a significant focus within cancer therapeutics research. Nonetheless, the efficiency of antigen presentation in tumor vaccine remains suboptimal. We introduce an innovative mRNA-lipid nanoparticle platform designed to express tumor antigenic epitopes fused with the transmembrane domain and cytoplasmic tail of the neonatal Fc receptor (FcRn). This novel design exploits FcRn trafficking signals to direct the epitope-FcRn fusion toward endolysosomal degradation, thereby generating epitopes capable of eliciting targeted T cell responses and establishing immune memory. The FcRn-directed presentation of epitopes enhances MHC class I and II antigen presentation, thereby robustly inducing CD4⁺ and CD8⁺ T cell responses, which translates to the inhibition of tumor growth and extension of survival in preclinical mouse models. In summary, the deliberate incorporation of FcRn trafficking signals into vaccine design markedly boosts T cell responses, underscoring the promise of this novel strategy in advancing the efficacy of tumor vaccines.</p>","PeriodicalId":9595,"journal":{"name":"Cancer Immunology, Immunotherapy","volume":"74 2","pages":"54"},"PeriodicalIF":4.6,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11699006/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142920484","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 PD-1 blockade-activated neoantigen specific cellular therapy for advanced relapsed non-small cell lung cancer.","authors":"Yun Qiao, Kaiyuan Hui, Chenxi Hu, Mei Wang, Wen Sun, Liang Liu, Changhong Dong, Xiaodong Jiang","doi":"10.1007/s00262-024-03906-z","DOIUrl":"10.1007/s00262-024-03906-z","url":null,"abstract":"<p><strong>Background: </strong>Due to its strong immunogenicity and tumor specificity, neoplastic antigen has emerged as an immunotherapy target with wide therapeutic prospect and clinical application value. Anti-programmed death-1 (PD-1) antibodies reinvigorate T cell-mediated antitumor immunity. So, we conducted single-arm trial to assess the safety and efficacy of PD-1 blockade(Camrelizumab)-activated neoantigen specific cellular therapy (aNASCT) on advanced relapsed non-small lung cancer(NSCLC)(ClinicalTrials.gov NCT03205930).</p><p><strong>Methods: </strong>Neoantigenic peptides were designed and manufactured according to the whole exome sequencing and RNA sequencing of fresh biopsy tissues and peripheral blood as well as bioinformatics analysis. All participants received subcutaneous injection of mature dendritic cells(mDCs) loaded with neoantigens on day 8 and an intravenous infusion of PD-1 blockade-activated autologous cytotoxic T lymphocytes (CTLs) induced by mDCs on day 27 for a period defined as 28 days (4 weeks). Enrolled patients received at least three cycles of therapy. The safety and efficacy of the treatment were evaluated by evaluating adverse reactions, progression-free survival (PFS), overall survival (OS).</p><p><strong>Results: </strong>A total of 13 patients with advanced relapsed NSCLC were enrolled in this study. All 13 patients received at least three cycles of aNASCT treatment, of which two patients received at most 12 cycles of treatment. Treatment-related adverse events (AEs) occurred in 4/13 (30.8%)patients with transient fever below 38℃.The objective response rate (ORR) across the 13 enrolled patients was 7 of 13 (53.85%,95% CI 0.29-0.77).The disease control rate (DCR) was 8 of 13 (61.54%,95% CI 0.36-0.82). The median PFS was 11 months (95% CI 6.1-15.9), and the median OS was 15 months(95% CI 11.5-18.5).</p><p><strong>Conclusions: </strong>Our findings indicate that aMASCT therapy was safety and immunogenicity of patients with advanced relapsed NSCLC, suggesting its promising potential in cancer immunotherapy.</p>","PeriodicalId":9595,"journal":{"name":"Cancer Immunology, Immunotherapy","volume":"74 2","pages":"60"},"PeriodicalIF":4.6,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11699067/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142920475","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 nivolumab and ipilimumab with or without chemotherapy for unresectable non-small cell lung cancer: a multicenter retrospective observational study.","authors":"Toshiyuki Sumi, Yutaro Nagano, Keiki Yokoo, Tatsuru Ishikawa, Hirotaka Nishikiori, Osamu Honjo, Sayaka Kudo, Masami Yamazoe, Shun Kondoh, Makoto Shioya, Mitsuo Otsuka, Midori Hashimoto, Hayato Yabe, Yusuke Tanaka, Yuta Sudo, Masahiro Yanagi, Mamoru Takahashi, Hirofumi Chiba","doi":"10.1007/s00262-024-03890-4","DOIUrl":"10.1007/s00262-024-03890-4","url":null,"abstract":"<p><strong>Introduction: </strong>Compared to platinum-based therapies, a combination of ipilimumab (anti-CTLA-4) and nivolumab (anti-PD-1) has demonstrated improved outcomes in advanced non-small cell lung cancer (NSCLC), albeit with higher rates of immune-related adverse events (irAEs). This multicenter retrospective study evaluated the efficacy and safety of nivolumab and ipilimumab with or without chemotherapy (NI and NICT) in real-world clinical settings.</p><p><strong>Methods: </strong>We enrolled 215 treatment-naïve NSCLC patients who received NI or NICT between December 2020 and May 2023 at 14 institutions in Japan. Severe irAEs (Grade ≥ 3) were assessed using the Common Terminology Criteria for Adverse Events. Progression-free survival (PFS) and overall survival (OS) were evaluated using Kaplan-Meier methods and propensity score matching.</p><p><strong>Results: </strong>Of 215 patients, 104 and 111 received NI and NICT, respectively. The median PFS was 5.3 and 5.9 months for NI and NICT, respectively. The median OS was 22.1 and 19.2 months for NI and NICT, respectively. High fever within 3 weeks of treatment initiation and high tumor burden were indicators of severe irAEs. Grade 3 or higher irAEs occurred in 36.5% patients in the NI group and 50.5% patients in the NICT group, with higher treatment-related mortality in the NICT group (5.4% vs. 1.9% in NI).</p><p><strong>Conclusions: </strong>NI and NICT showed comparable efficacies in PFS and OS. However, NICT had a higher incidence of severe irAEs and treatment-related mortality. High tumor burden and early high fever were predictors of severe irAEs. Further research is warranted to optimize the efficacy and safety of NICT for NSCLC treatment.</p>","PeriodicalId":9595,"journal":{"name":"Cancer Immunology, Immunotherapy","volume":"74 2","pages":"39"},"PeriodicalIF":4.6,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11698699/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142920375","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 correlation between LAG-3 expression and the efficacy of chemoimmunotherapy in advanced biliary tract cancer.","authors":"Cheng-Yu Tang, Yi-Ting Lin, Yi-Chen Yeh, Shin-Yi Chung, Yu-Chan Chang, Yi-Ping Hung, San-Chi Chen, Ming-Huang Chen, Nai-Jung Chiang","doi":"10.1007/s00262-024-03878-0","DOIUrl":"10.1007/s00262-024-03878-0","url":null,"abstract":"<p><p>In our previous phase II T1219 trial for advanced biliary tract cancer (ABTC), the combination of nivolumab with modified gemcitabine and S-1 exhibited promising efficacy, while the programmed-death-ligand-1 (PD-L1) expression did not predict chemoimmunotherapy efficacy. Lymphocyte-activation-gene-3 (LAG-3), a negative immune checkpoint, is frequently co-expressed with PD-L1. This study assessed the predictive value of LAG-3 expression in ABTC patients who received chemoimmunotherapy. We analyzed 44 formalin-fixed ABTC samples using immunohistochemical staining for PD-L1 and LAG-3 and correlated them with the clinical efficacy of chemoimmunotherapy. Digital spatial profiling was conducted in selected regions of interest to examine immune cell infiltration and checkpoint expression in six cases. Three public BTC datasets were used for analysis: TCGA-CHOL, GSE32225, and GSE132305. LAG-3 positivity was observed in 38.6% of the ABTC samples and was significantly correlated with PD-L1 positivity (P < 0.001). The objective response rate (ORR) was significantly higher in LAG-3-positive tumors than in LAG-3-negative tumors (70.6% vs. 33.3%, P = 0.029). The LAG-3 expression level was associated with an increased ORR (33%, 58%, and 100% for LAG-3 < 1%, 1-9%, and ≥ 10%, respectively; P = 0.018) and a deeper therapeutic response (20.1%, 38.6%, and 57.6% for the same respective groups; P = 0.04). LAG-3 expression is positively correlated with the expression of numerous immune checkpoints. Enrichment of CD8⁺ T cells was observed in LAG-3-positive BTC, indicating that LAG-3 expression may serve as a biomarker for identifying immune-inflamed tumors and predicting the therapeutic response to chemoimmunotherapy in ABTC.</p>","PeriodicalId":9595,"journal":{"name":"Cancer Immunology, Immunotherapy","volume":"74 2","pages":"41"},"PeriodicalIF":4.6,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11699023/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142920696","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":"Anti-PD1-/PDL1-induced chronic intestinal pseudo-obstruction: three cases treated with vedolizumab after corticosteroid failure with mixed results.","authors":"Morgan Zenatri, Michael Collins, Tifanie Alberto, Antonio Farina, Sophie Collardeau-Frachon, Mélanie Saint-Jean, François Bocquet, Frederic Dumont, Jérôme Honnorat, Bastien Joubert, Judith Raimbourg","doi":"10.1007/s00262-024-03901-4","DOIUrl":"10.1007/s00262-024-03901-4","url":null,"abstract":"<p><p>Immune checkpoint inhibitors (ICI), i.e., anti-PD1/PDL1 and anti-CTLA-4, have reshaped the prognosis of many cancers. Increased use of ICI has led to the onset of new adverse events. Neurological immune-related adverse events are rare, heterogenous, and potentially life-threatening. Chronic intestinal pseudo-obstruction (CIPO) is an immune-related autonomic plexus neuropathy that may be caused by infiltration of the myenteric plexus by CD8 + T cells. It is a rare and potentially fatal side effect that can be difficult to diagnose early because of initial nonspecific clinical presentation including vomiting, nausea, diarrhea, and constipation. Some rare cases have been described in the literature reporting a frequent resistance to corticosteroids making it necessary to use other immunosuppressive therapy. Vedolizumab is an antibody (Ab) blocking integrin α4-β7 used to treat inflammatory bowel disease. We report the first three cases of ICI-induced CIPO-treated with vedolizumab after corticosteroid failure, with very limited benefits (only one patient with transitory improvement). Based on our results in three cases, vedolizumab does not currently appear to be a therapeutic option. Earlier administration with a standardized dose and frequency schedule may provide better outcomes.</p>","PeriodicalId":9595,"journal":{"name":"Cancer Immunology, Immunotherapy","volume":"74 2","pages":"45"},"PeriodicalIF":4.6,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11699004/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142920897","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":"First-line immune-based combinations or sunitinib in favorable-risk metastatic renal cell carcinoma: a real-world retrospective comparison from the ARON-1 study.","authors":"Giandomenico Roviello, Javier Molina-Cerrillo, Francesco Massari, Linda Cerbone, Ondrej Fiala, Giuseppe Fornarini, Fernando Sabino Marques Monteiro, Carlo Cattrini, Johannes Landmesser, Carlo Messina, Anca Zgura, Sara Elena Rebuzzi, Andrey Soares, Francesco Carrozza, Jawaher Ansari, Francesco Grillone, Zsófia Küronya, Lorena Incorvaia, Dipen Bhuva, Cinzia Ortega, Cecilia Nasso, Ravindran Kanesvaran, Ilaria Zampiva, Camillo Porta, Sebastiano Buti, Matteo Santoni","doi":"10.1007/s00262-024-03897-x","DOIUrl":"10.1007/s00262-024-03897-x","url":null,"abstract":"<p><strong>Introduction: </strong>Renal cell carcinoma (RCC) is one of the most common types of urogenital cancer. The introduction of immune-based combinations, including dual immune-checkpoint inhibitors (ICI) or ICI plus tyrosine kinase inhibitors (TKIs), has radically changed the treatment landscape for metastatic RCC, showing varying efficacy across different prognostic groups based on the International Metastatic RCC Database Consortium (IMDC) criteria.</p><p><strong>Materials and methods: </strong>This retrospective multicenter study, part of the ARON-1 project, aimed to evaluate the outcomes of favorable-risk metastatic RCC patients treated with immune-based combinations or sunitinib. Patients were assessed for overall survival (OS), progression-free survival (PFS) and overall response rate. We carried out a survival analysis by a Cox regression model.</p><p><strong>Results: </strong>A total of 524 favorable-risk patients were included in the analysis. After a median follow-up of 37.2 months, the median OS in the overall population was 56.1 months. There was no significant difference in OS between patients receiving sunitinib and those receiving TKI + ICI combinations (p = 0.761). Patients on TKI + ICI had significantly longer PFS compared to patient treated with sunitinib (30.7 vs 22.9 months, p = 0.007). Analysis of OS and PFS based on metastatic site revealed that patients with bone metastases benefited more from ICI plus TKI (56 patients with bone metastases receiving IO + TKI, 38 received pembrolizumab plus axitinib, 15 cabozantinib plus nivolumab and 3 pembrolizumab plus lenvatinib), while sunitinib was more effective for pancreatic and glandular metastases. Additionally, the number of metastatic sites played a role, with TKI plus ICI showing superiority in patients with a single metastatic site. The time from RCC diagnosis to metastatic disease also impacted outcomes, with TKI plus ICI being more effective in patients with a shorter interval (i.e., < 36 months).</p><p><strong>Conclusions: </strong>The choice between upfront combination or monotherapy for metastatic favorable prognosis RCC remains a current issue. While combination therapy offers prolonged PFS, it does not necessarily translate to improve OS compared to sunitinib. This real-world study supports the superiority in terms of PFS of TKI plus ICI vs TKI monotherapy but not in OS. Probable, other clinical factors should be taking into account to make clinical treatment decisions in this setting.</p>","PeriodicalId":9595,"journal":{"name":"Cancer Immunology, Immunotherapy","volume":"74 2","pages":"65"},"PeriodicalIF":4.6,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11699065/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142920489","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":"Transferrin receptor uptakes iron from tumor-associated neutrophils to regulate invasion patterns of OSCC.","authors":"Qian Si, Yuhan Wang, Wanqiu Lu, Zijian Liu, Yuxian Song, Sheng Chen, Shu Xia, Huiling Li, Pei Weng, Yue Jing, Qiuya Yu, Feng Zhu, Xiaoxin Zhang, Xiaofeng Huang, Yanhong Ni","doi":"10.1007/s00262-024-03894-0","DOIUrl":"10.1007/s00262-024-03894-0","url":null,"abstract":"<p><strong>Background: </strong>Transferrin receptor (TFRC) uptakes iron-loaded transferrin (TF) to acquire iron and regulates tumor development. Nonetheless, the clinical values and the precise functions of TF-TFRC axis in the development of oral squamous cell carcinoma (OSCC) were still undiscovered, especially the impacts of their regional heterogeneous expression.</p><p><strong>Methods: </strong>Immunohistochemistry (IHC) was used to analyze the expression of TFRC in 106 OSCC patients. Then the prognostic value of TFRC was compared between high and low worst pattern of invasion (WPOI) patients. OSCC cells with low or high expression of TFRC were constructed, and functional experiments were performed to elucidate the effects of TFRC on the migration and proliferation of OSCC cells. Multi-immunofluorescence was applied to stain TF and tumor-associated neutrophils (TANs). The stimulating effects of TF were compared between normal and high TFRC cells in vitro and across different OSCC patients' subgroups in our sample bank and TCGA database.</p><p><strong>Results: </strong>Higher TFRC was expressed at invasive tumor front (ITF) in OSCC and correlated with WPOI. Only at ITF in patients with WPOI 4-5, TFRC was a prognostic factor. High TFRC promoted migration and proliferation of cancer cells. Additionally, TANs secreted TF outside. Exogenous TF promoted migration and proliferation of cells with high expression of TFRC. Compared to the TANs^lowTFRC^low OSCC patients, TANs^highTFRC^high OSCC patients had poorer clinical outcomes.</p><p><strong>Conclusions: </strong>Higher expression of TFRC at ITF and TANs-TF-TFRC axis promoted OSCC invasion at ITF by facilitating cell migration and proliferation, which may result from increased cellular iron uptake through regulating iron metabolism.</p>","PeriodicalId":9595,"journal":{"name":"Cancer Immunology, Immunotherapy","volume":"74 2","pages":"43"},"PeriodicalIF":4.6,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11699170/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142920762","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":"Tertiary lymphoid structures in high-grade serous tubo-ovarian carcinoma: anatomical site matters.","authors":"Sofia Westbom-Fremer, Lena Tran, Anna Ebbesson, Laura Martin de la Fuente, Jenny-Maria Jönsson, Päivi Kannisto, Srinivas Veerla, Ingrid Hedenfalk","doi":"10.1007/s00262-024-03911-2","DOIUrl":"10.1007/s00262-024-03911-2","url":null,"abstract":"<p><p>Tertiary lymphoid structures (TLS) in the tumor microenvironment are prognostically beneficial in many solid cancer types. Reports on TLS in high-grade serous tubo-ovarian carcinoma (HGSC) are few, and the prognostic impact is unclear. We investigated mature TLS (mTLS), immature TLS (iTLS) and lymphoid aggregates (LA) in primary adnexal tumors (PTs) and synchronous omental/peritoneal metastases (pMets) of HGSC. Whole H&E slides were scrutinized for mTLS and LA in a population-based cohort of 130 cases with stage III-IV HGSC. The immune cell tumor infiltration was evaluated with single chromogenic immunohistochemistry (IHC) on a tissue microarray (TMA) from the same cases. Selected whole slides (PT n = 11, pMet n = 10) of the cases most abundant in mTLS and LA were further investigated with multiplex IHC and immunofluorescence using digital image analysis (QuPath), to confirm TLS status and map the T and B lymphocyte subtypes. The results showed that mTLS were more common in pMets than in PTs but did not have an independent prognostic impact on overall or progression-free survival. The presence of mTLS correlated with intratumoral infiltration of CD8⁺ cytotoxic T cells, FOXP3⁺ regulatory T cells and PD-1⁺ lymphocytes in pMets only. Although overall mTLS cell composition was similar between PTs and pMets, the outer zones of mTLS in PTs were more immune cell-rich. In conclusion, our results indicate differences in TLS presence and cellular elements between primary adnexal tumors and synchronous peritoneal metastases, which are important to consider when conducting studies of the immune environment in HGSC.</p>","PeriodicalId":9595,"journal":{"name":"Cancer Immunology, Immunotherapy","volume":"74 2","pages":"56"},"PeriodicalIF":4.6,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11699021/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142920731","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":"Role of the HGF/c-MET pathway in resistance to immune checkpoint inhibitors in advanced non-small cell lung cancer.","authors":"Assya Akli, Paul Takam Kamga, Catherine Julie, Claude Capron, Adrien Costantini, Coraline Dumenil, Jennifer Dumoulin, Violaine Giraud, Florence Parent, Andrei Seferian, Catherine Guettier, Mathieu Glorion, Elisabeth Longchampt, Jean-François Emile, Étienne Giroux-Leprieur","doi":"10.1007/s00262-024-03882-4","DOIUrl":"10.1007/s00262-024-03882-4","url":null,"abstract":"<p><p>Most of advanced non-small cell lung cancer (NSCLC) patients will experience tumor progression with immunotherapy (IO). Preliminary data suggested an association between high plasma HGF levels and poor response to IO in advanced NSCLC. Our study aimed to evaluate further the role of the HGF/MET pathway in resistance to IO in advanced NSCLC. We included retrospectively 82 consecutive NSCLC patients from two academic hospitals. Among them, 49 patients received ICIs alone or in combination with chemotherapy (CT), while 33 patients received chemotherapy alone as the control group. We analyzed plasma HGF levels by ELISA and expression of PD-L1, MET/phospho-MET, and CD8+ T-Cell infiltration on lung tumor tissue by immunohistochemistry. We investigated the contribution of HGF/MET to IO response by culturing peripheral blood mononuclear cells (PBMC) with or without pembrolizumab, with recombinant HGF, or cocultured with NSCLC patients-derived explants. Additionally, c-MET inhibitors were used to evaluate the contribution of MET activation in NSCLC-mediated immunosuppression. High HGF levels were associated with high progression rate with IO (p = 0.0092), but not with CT. ELISA analysis of supernatants collected from cultured NSCLC cells showed that HGF was produced by tumor cells. Furthermore, when activated PBMCs were cultured in the presence of recombinant HGF or on NSCLC monolayer, the proliferation of CD3+CD8+ lymphocytes was inhibited, even in the presence of pembrolizumab. The addition of HGF/MET inhibitors restored lymphocyte activation and induced IFNγ production. In conclusion, inhibiting the HGF/MET signaling pathway could be a promising approach to enhance the efficacy of immunotherapy.</p>","PeriodicalId":9595,"journal":{"name":"Cancer Immunology, Immunotherapy","volume":"74 2","pages":"58"},"PeriodicalIF":4.6,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11698708/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142920657","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}