Cancer Immunology, Immunotherapy最新文献

{"title":"KLF12 as a potential biomarker for lateral pelvic lymph node metastases in advanced rectal cancer.","authors":"Tianxian Xiao, Fangze Wei, Sicheng Zhou, Fuqiang Zhao, Fei Huang, Liu Qian","doi":"10.1007/s00262-025-03991-8","DOIUrl":"10.1007/s00262-025-03991-8","url":null,"abstract":"<p><p>Rectal cancer accounts for approximately 40% of colorectal cancer cases, and lateral pelvic lymph node (LPLN) metastasis in rectal cancer significantly increases the local recurrence rate. Despite its clinical significance, studies on the molecular biology of LPLN metastasis are relatively scarce. In this study, we aimed to elucidate the underlying mechanisms by identifying hub regulatory genes in LPLN tissues and analyzing differentially expressed genes shared between tumor and pericarcinomatous tissues within our clinical cohort. To investigate the biological functions of these hub regulatory genes, we performed GSEA, GO, and KEGG pathway analyses on mRNA-Seq data. Among the identified hub genes, KLF12 emerged as a pivotal regulatory gene in rectal cancer. We further explored its clinical relevance and biological function. Our findings, validated using public databases, clinical cohort data, and immunohistochemistry (IHC), identified KLF12 as a specific marker for LPLN. Additionally, KLF12 expression exhibited a strong correlation with disease-free survival (DFS). According to clinical data, significant differences in KLF12 expression exist between groups based on factors such as age, gender, tumor location, pathological N stage, and postoperative tumor residue. Both treatment outcomes (DFS) and receiver operating characteristic curves (AUCs) were significantly associated with KLF12 expression. Furthermore, KLF12 demonstrated a strong association with immune cell infiltration, immune checkpoint expression, and immunophenoscore (IPS), indicating its potential regulatory role in immunotherapy. Functional molecular experiments revealed that KLF12 overexpression inhibited the proliferation, migration, and invasion of SW620 cells. In conclusion, leveraging mRNA-Seq data, TCGA database analysis, immune infiltration data, and biological function assessments, we confirmed that KLF12 could serve as an effective predictive marker and potential therapeutic target for LPLN metastasis. These findings suggest that KLF12 may be instrumental in assessing predictive risk and identifying novel therapeutic targets for patients with rectal cancer.</p>","PeriodicalId":9595,"journal":{"name":"Cancer Immunology, Immunotherapy","volume":"74 7","pages":"199"},"PeriodicalIF":4.6,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12075072/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143980382","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":"Recombinant antibodies from clonally expanded cancer-associated plasma cells.","authors":"Wonkyung Kim, Ji-Hye Oh, Chae Won Park, Hyori Kim, Young Gwang Kang, Da Eun Oh, Hee Jin Lee, Ji Hun Kim, Chang Ohk Sung","doi":"10.1007/s00262-025-04045-9","DOIUrl":"10.1007/s00262-025-04045-9","url":null,"abstract":"<p><p>Although the clinical significance of plasma cells within tumors has been recognized, studies on the development of plasma cells and the characteristics of the antibodies they secrete within the tumor microenvironment remain limited. We investigated the properties of plasma cells within cancer tissues using single-cell RNA and single cell B cell receptor sequencing. We characterized plasma cells exhibiting clonal expansion and synthesized the antibodies produced by these cells, confirming the clinical relevance of immunoglobulin H (IGH) isotypes. Plasma cells comprised approximately 5% of the total immune cell population within the tumor; clonal expansion was more prevalent in plasma cells than in B cells. Among plasma cells, the most frequent immunoglobulin isotype was IGHG1 and IGKC. We synthesized six recombinant antibodies, including those from the largest clonal plasma cells. Two antibodies that formed clones showed membranous staining in cancer cells. The cancer cells that metastasized to the lymph node showed a loss of expression as observed by immunohistochemistry. Analysis of bulk RNA sequencing data from 1078 patients with breast cancer revealed that tumor-infiltrating plasma cells expressing IGHG1 were associated with favorable prognoses. These tumors exhibited increased B cell receptor diversity, immunogenic mutation, and intratumoral heterogeneity. This study suggests the potential for discovering cancer-associated antibodies derived from intratumoral plasma cells.</p>","PeriodicalId":9595,"journal":{"name":"Cancer Immunology, Immunotherapy","volume":"74 7","pages":"201"},"PeriodicalIF":4.6,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12075076/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143981166","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":"Characterization of the aryl hydrocarbon receptor as a potential candidate to improve cancer T cell therapies.","authors":"Valentine De Castro, Oumaïma Abdellaoui, Barbara Dehecq, Babacar Ndao, Patricia Mercier-Letondal, Alexandra Dauvé, Francine Garnache-Ottou, Olivier Adotévi, Romain Loyon, Yann Godet","doi":"10.1007/s00262-025-04065-5","DOIUrl":"10.1007/s00262-025-04065-5","url":null,"abstract":"<p><p>The efficacy of T-cell-based cancer therapies can be limited by the tumor microenvironment which can lead to T cell dysfunction. Multiple studies, particularly in murine models, have demonstrated the capacity of the aryl hydrocarbon receptor (AHR) to negatively regulate antitumor T cell functions. AHR is a cytoplasmic receptor and transcription factor that was originally identified as a xenobiotic sensor, but has since been shown to play a significant role in the gene regulation of various immune cells, including T cells. Given the insights from murine studies, AHR emerges as a promising candidate to invalidate for optimizing T cell-based cancer therapies. However, the controversial role of AHR in human T cells underscores the need for a more comprehensive characterization of AHR expressing T cells. This study aims to investigate the regulatory mechanisms of AHR in human T cell biology to better understand its impact on reducing antitumor immune responses. Here, we knocked-out AHR in human T cells using CRISPR-Cas9 technology to characterize AHR's function in an in vitro chronic stimulation model. Engineered T cells exhibited enhanced effector- and memory-like profiles and expressed reduced amount of CD39 and TIGIT. AHR knockout enhanced human CAR-T cells' functionality and persistence upon tumor chronic stimulation. Collectively, these results highlight the role of AHR in human CAR-T cells efficiency.</p>","PeriodicalId":9595,"journal":{"name":"Cancer Immunology, Immunotherapy","volume":"74 7","pages":"200"},"PeriodicalIF":4.6,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12075070/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143953567","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":"Knockdown NEK7 stimulates anti-tumor immune responses by NLRP3/PD-L1 signaling in esophageal cancer.","authors":"Li Wang, Yurong Cheng, Weiqiang Li, Jing Wang, Zhe Liu, Yaoxian Xiang, Xin Liu, Kangjie Wang, Dong Yan","doi":"10.1007/s00262-025-04057-5","DOIUrl":"https://doi.org/10.1007/s00262-025-04057-5","url":null,"abstract":"<p><strong>Background: </strong>Esophageal cancer is a prevalent malignancy with limited treatment options. The study aimed to understand the role and mechanism of NEK7 in esophageal cancer development.</p><p><strong>Methods: </strong>RNA sequencing compared esophageal cancer tissues with adjacent tissues, and real-time PCR validated NEK7 expression. Co-IP identified NLRP3 as NEK7's binding partner. We also study the effects of NEK7 knockdown on cell viability, apoptosis, migration, invasion, and the expression of NLRP3/PD-L1 in esophageal carcinoma cell lines. TIMER 2.0 analyzed immune infiltration. An animal model was used to investigate the impact of NEK7 knockdown on tumor size, survival rates, and immune cell infiltration. Licochalcone B blocked NEK7/NLRP3, enhancing CD8 T cell-mediated tumor killing. PD-1's role in T cell viability was also assessed.</p><p><strong>Results: </strong>NEK7 was observed to be markedly elevated in both tumor tissues of esophageal cancer and EC109 cells. Moreover, silencing NEK7 reduced cell viability, migration, and invasion, while enhancing cell apoptosis in vitro. Knockdown of NEK7 caused a notable reduction in levels of NLRP3 and PD-L1 in EC109 cells. NEK7 expression showed a positive correlation with immune cell infiltration. Knockdown of NEK7 decreased PD-L1 expression, while upregulation of NEK7 increased PD-L1 expression, then reversed by NLRP3 knockdown. In animal studies, NEK7 knockdown reduced tumor size and volume while improving survival. It also promoted CD4 and CD8 T cell infiltration while inhibiting Treg cells and PD-1 + CD4 and CD8 T cells. Licochalcone B blocked NEK7/NLRP3 binding, decreased cell viability of EC109 cells, and enhanced the activity of co-cultured CD8 T cells. Furthermore, Licochalcone B and anti-PD-1 treatment increased the killing ratio of EC109 cells.</p><p><strong>Conclusion: </strong>In conclusion, NEK7 is a key regulator in the progression of esophageal cancer and the immune evasion. Targeting the NEK7/NLRP3 pathway may have therapeutic potential for the treatment of esophageal cancer.</p>","PeriodicalId":9595,"journal":{"name":"Cancer Immunology, Immunotherapy","volume":"74 7","pages":"197"},"PeriodicalIF":4.6,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12065700/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144062450","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 combination of SH003 and DTX induces cytotoxic cell infiltration in anti-PD1 resistant lung cancer.","authors":"Yu-Jeong Choi, Sang-Eun Lee, Daeun Kim, Hae-In Lim, Da Kyung Choi, Bong Kyu Park, Chan-Yong Jeon, Seong-Gyu Ko","doi":"10.1007/s00262-025-04064-6","DOIUrl":"https://doi.org/10.1007/s00262-025-04064-6","url":null,"abstract":"<p><p>The development of therapeutic strategies to overcome resistance to anti-PD1 therapies in lung cancer remains a significant challenge. Based on our recent findings of SH003's immunomodulatory capabilities, this study investigates the combined effects of SH003 and docetaxel (DTX) as a potential second-line therapy in an anti-PD1-resistant lung cancer model. Our results demonstrate that SH003 and DTX effectively inhibit tumor growth by inducing apoptosis in an anti-PD1-resistant lung cancer LLC1 model, while enhancing the infiltration of cytotoxic CD8⁺ T cells and NK cells into the tumor microenvironment (TME), thereby boosting anti-tumor immunity. SH003 also exhibited immunomodulatory effects in an immunosuppressed mouse model, further emphasizing its potential in enhancing immune responses. Notably, the combination treatment significantly inhibits tumor growth by targeting the EGFR/JAK/STAT3 signaling pathway, contributing to the reduction of PD-L1 expression associated with immune evasion. These findings elucidate the dual mechanism of action of the SH003-DTX combination in overcoming resistance through both direct anticancer effects and immune system modulation. Overall, these findings demonstrate that the SH003-DTX combination presents a promising approach for anti-PD1-refractory lung cancer patients, potentially offering new treatment possibilities where current options are limited.</p>","PeriodicalId":9595,"journal":{"name":"Cancer Immunology, Immunotherapy","volume":"74 7","pages":"198"},"PeriodicalIF":4.6,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12065697/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143964304","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":"Pembrolizumab plus Lenvatinib in patients with metastatic Renal Cell Carcinoma: real-world evidences from the international ARON- 1 study.","authors":"Camillo Porta, Francesco Massari, Tarek Taha, Enrique Grande, Maria T Bourlon, Ravindran Kanesvaran, Umberto Basso, Javier Molina-Cerrillo, Teresa Alonso-Gordoa, Zin W Myint, Giuseppe Fornarini, Thomas Buttner, Se Hoon Park, Yüksel Ürün, Ugo De Giorgi, Renate Pichler, Pasquale Rescigno, Tomas Buchler, Hana Studentova, Bohuslav Melichar, Jawaher Ansari, Veronica Mollica, Jakub Kucharz, Mimma Rizzo, Alessandro Rizzo, Ray Manneh Kopp, Sebastiano Buti, Fernando Sabino Marques Monteiro, Andrey Soares, Aristotelis Bamias, Matteo Santoni","doi":"10.1007/s00262-025-04019-x","DOIUrl":"https://doi.org/10.1007/s00262-025-04019-x","url":null,"abstract":"<p><strong>Background: </strong>Pembrolizumab plus lenvatinib is a treatment option for metastatic Renal Cell Carcinoma (mRCC). In the ARON-1 study we investigated we the real-world experiences gained from the use of this combination for mRCC.</p><p><strong>Methods: </strong>We retrospectively investigated real-world clinical outcomes of mRCC patients receiving pembrolizumab plus lenvatinib within the ARON-1 study. Overall survival (OS) was calculated from the start of pembrolizumab plus lenvatinib to death for any cause. Progression-Free Survival (PFS) was defined as the time from the start of pembrolizumab to progression or death from any cause. Duration of response (DoR) was defined as the time from the start of pembrolizumab to disease progression or death, whichever occurred first, in patients who achieved complete remission (CR) or partial response (PR). Overall Response Rate (ORR) was defined as the proportion of patients who achieve a CR or PR per RECIST criteria. Adverse events were retrospectively collected from electronic and paper charts and categorized by the Common Terminology Criteria for Adverse Events (CTCAE) v5.0.</p><p><strong>Results: </strong>Overall, we included 202 mRCC patients treated with pembrolizumab plus lenvatinib. The median follow-up time was 15.1 months. The median OS was not reached (NR), with a median PFS of 25.6 months and an Overall Response Rate (ORR) of 59%. The median Duration of Response (DoR) was 26.2 months. G3-G4 adverse events (AEs) were observed in 92 patients (46%), with hypertension being the most common AE (13%).</p><p><strong>Conclusions: </strong>Pembrolizumab plus lenvatinib is an effective and tolerable treatment for mRCC also in the real-world setting.</p>","PeriodicalId":9595,"journal":{"name":"Cancer Immunology, Immunotherapy","volume":"74 7","pages":"196"},"PeriodicalIF":4.6,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12064502/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143970731","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":"Extracellular PKM2 modulates cancer immunity by regulating macrophage polarity.","authors":"Guangda Peng, Bin Li, Hongwei Han, Yi Yuan, Falguni Mishra, Yang Huang, Zhi-Ren Liu","doi":"10.1007/s00262-025-04050-y","DOIUrl":"https://doi.org/10.1007/s00262-025-04050-y","url":null,"abstract":"<p><p>Tumor controls its immunity by educating its microenvironment, including regulating polarity of tumor associated macrophages. It is well documented that cancer cells release PKM2 to facilitate tumor progression. We report here that the extracellular PKM2 (EcPKM2) modulates tumor immunity by facilitating M2 macrophage polarization in tumors. EcPKM2 interacts with integrin α_vβ₃ on macrophage to activate integrin-FAK-PI3K signal axis. Activation of FAK-PI3K by EcPKM2 suppresses PTEN expression, which subsequently upregulates arginase1 (Arg1) expression and activity in macrophage to facilitate M2 polarity. Our studies uncover a novel and important mechanism for modulation of tumor immunity. More importantly, an antibody against PKM2 that disrupts the interaction between EcPKM2 and integrin α_vβ₃ is effective in converting M2 macrophages to M1 macrophages in tumors, suggesting a new therapeutic strategy and target for cancer therapies. Combination of the anti-PKM2 antibody with checkpoint blockades provides enhanced treatment effects.</p>","PeriodicalId":9595,"journal":{"name":"Cancer Immunology, Immunotherapy","volume":"74 7","pages":"195"},"PeriodicalIF":4.6,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12064527/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143961695","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":"HIF-PH inhibitors induce pseudohypoxia in T cells and suppress the growth of microsatellite stable colorectal cancer by enhancing antitumor immune responses.","authors":"Yuehua Chen, Toshiaki Ohara, Yusuke Hamada, Yuze Wang, Miao Tian, Kazuhiro Noma, Hiroshi Tazawa, Masayoshi Fujisawa, Teizo Yoshimura, Akihiro Matsukawa","doi":"10.1007/s00262-025-04067-3","DOIUrl":"https://doi.org/10.1007/s00262-025-04067-3","url":null,"abstract":"<p><strong>Background: </strong>Recent studies have revealed that CD8⁺ T cells can be activated via genetic upregulation of HIF-1α, thereby augmenting antitumor effector functions. HIF-1α upregulation can be attained by inhibiting HIF-prolyl hydroxylase (HIF-PH) under normoxic conditions, termed pseudohypoxia. This study investigated whether pseudohypoxia induced by HIF-PH inhibitors suppresses Microsatellite stable (MSS) colorectal cancer (CRC) by affecting tumor immune response.</p><p><strong>Methods: </strong>The HIF-PH inhibitors Roxadustat and Vadadustat were utilized in this study. In vitro, we assessed the effects of HIF-PH inhibitors on human and murine colon cancer cell lines (SW480, HT29, Colon26) and murine T cells. In vivo experiments were performed with mice bearing Colon26 tumors to evaluate the effect of these inhibitors on tumor immune responses. Tumor and spleen samples were analyzed using immunohistochemistry, RT-qPCR, and flow cytometry to elucidate potential mechanisms.</p><p><strong>Results: </strong>HIF-PH inhibitors demonstrated antitumor effects in vivo but not in vitro. These inhibitors enhanced the tumor immune response by increasing the infiltration of CD8⁺ and CD4⁺ tumor-infiltrating lymphocytes (TILs). HIF-PH inhibitors induced IL-2 production in splenic and intratumoral CD4⁺ T cells, promoting T cell proliferation, differentiation, and immune responses. Roxadustat synergistically enhanced the efficacy of anti-PD-1 antibody for MSS cancer by increasing the recruitment of TILs and augmenting effector-like CD8⁺ T cells.</p><p><strong>Conclusion: </strong>Pseudohypoxia induced by HIF-PH inhibitors activates antitumor immune responses, at least in part, through the induction of IL-2 secretion from CD4⁺ T cells in the spleen and tumor microenvironment, thereby enhancing immune efficacy against MSS CRC.</p>","PeriodicalId":9595,"journal":{"name":"Cancer Immunology, Immunotherapy","volume":"74 7","pages":"192"},"PeriodicalIF":4.6,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12064516/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143968106","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":"Osteosarcoma cell-derived CCL2 facilitates lung metastasis via accumulation of tumor-associated macrophages.","authors":"Hiroya Kondo, Hiroshi Tazawa, Tomohiro Fujiwara, Aki Yoshida, Miho Kure, Koji Demiya, Nobuhiko Kanaya, Toshiaki Hata, Koji Uotani, Joe Hasei, Toshiyuki Kunisada, Shunsuke Kagawa, Yusuke Yoshioka, Toshifumi Ozaki, Toshiyoshi Fujiwara","doi":"10.1007/s00262-025-04051-x","DOIUrl":"https://doi.org/10.1007/s00262-025-04051-x","url":null,"abstract":"<p><p>Osteosarcoma (OS) is the most common malignant tumor of bone in children and adolescents. Although lung metastasis is a major obstacle to improving the prognosis of OS patients, the underlying mechanism of lung metastasis of OS is poorly understood. Tumor-associated macrophages (TAMs) with M2-like characteristics are reportedly associated with lung metastasis and poor prognosis in OS patients. In this study, we investigated the metastasis-associated tumor microenvironment (TME) in orthotopic OS tumor models with non-metastatic and metastatic OS cells. Non-metastatic and metastatic tumor cells derived from mouse OS (Dunn and LM8) and human OS (HOS and 143B) were used to analyze the TME associated with lung metastasis in orthotopic OS tumor models. OS cell-derived secretion factors were identified by cytokine array and enzyme-linked immunosorbent assay (ELISA). Orthotopic tumor models with metastatic LM8 and 143B cells were analyzed to evaluate the therapeutic potential of a neutralizing antibody in the development of primary and metastatic tumors. Metastatic OS cells developed metastatic tumors with infiltration of M2-like TAMs in the lungs. Cytokine array and ELISA demonstrated that metastatic mouse and human OS cells commonly secreted CCL2, which was partially encapsulated in extracellular vesicles. In vivo experiments demonstrated that while primary tumor growth was unaffected, administration of CCL2-neutralizing antibody led to a significant suppression of lung metastasis and infiltration of M2-like TAMs in the lung tissue. Our results suggest that CCL2 plays a crucial role in promoting the lung metastasis of OS cells via accumulation of M2-like TAMs.</p>","PeriodicalId":9595,"journal":{"name":"Cancer Immunology, Immunotherapy","volume":"74 7","pages":"193"},"PeriodicalIF":4.6,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12064505/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143962035","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":"Clinical characteristics, outcomes, and predictive modeling of patients diagnosed with immune checkpoint inhibitor therapy-related pneumonitis.","authors":"Antonious Hazim, Irene Riestra Guiance, Jacob Shreve, Gordon Ruan, Damian McGlothlin, Allison LeMahieu, Robert Haemmerle, Keith Mcconn, Richard C Godby, Lisa Kottschade, Anna Schwecke, Casey Fazer-Posorske, Tobias Peikert, Eric Edell, Konstantinos Leventakos, Ashley Egan","doi":"10.1007/s00262-025-04053-9","DOIUrl":"https://doi.org/10.1007/s00262-025-04053-9","url":null,"abstract":"<p><strong>Purpose: </strong>The aim of this study is to better characterize the clinical characteristics and outcomes of patients diagnosed with Immune checkpoint Inhibitor (ICI) pneumonitis and propose predictive models.</p><p><strong>Patients and methods: </strong>Patients diagnosed with ICI pneumonitis at Mayo Clinic from 2014 to 2022 were studied. All cases were independently reviewed by our pulmonology specialist (A.E.) to confirm the appropriate diagnosis. The grading of pneumonitis was defined in accordance with ASCO guidelines (Schneider et al. in J Clin Oncol 39(36):4073-4126, 2021. https://doi.org/10.1200/JCO.21.01440 ). Predictive modeling was performed using gradient boosting machine learning technology, XGBoost (Chen in 1(4):1, 2015), to conduct binary classification and model reverse engineering using Shapley statistics (Lundberg and Lee in Adv Neural Inf Process Syst 30, 2017).</p><p><strong>Results: </strong>One hundred and seventy patients with ICI pneumonitis were included (median age 67; IQR 59, 75). Median overall survival was 2.3 years (95% CI: 1.8, NR). A higher grade of ICI pneumonitis was associated with inferior survival (HR 5.85, 95% CI: 2.27, 15.09; p < 0.001). Patients who were rechallenged with immunotherapy had significantly improved hazard of survival compared to patients not rechallenged (HR 0.37, 95% CI: 0.21, 0.68; p = 0.001). Risk of death from ICI pneumonitis prior to starting immunotherapy was modeled with an area under the curve of the receiver operator characteristic (AUC-ROC) of 0.79 with the most contributory features including peripheral blood lymphocyte count, oxygen dependence, pulmonary function testing, and PD-L1 expression.</p><p><strong>Conclusion: </strong>The presentation of ICI pneumonitis is highly variable, and outcomes are dependent on severity, but favor grade 2 disease when patients are rechallenged with immunotherapy. However, using commonly available clinical data, we can accurately identify patients at high risk of death from ICI pneumonitis. Further effort is needed to produce clinical models able to provide clinician decision support when evaluating patients with ICI toxicities and considering ICI rechallenge.</p>","PeriodicalId":9595,"journal":{"name":"Cancer Immunology, Immunotherapy","volume":"74 7","pages":"194"},"PeriodicalIF":4.6,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12064548/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143978866","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}