Cancer immunology, immunotherapy : CII最新文献

{"title":"Single-cell and multi-omics integration delineates the landscape of gene-wise intratumor heterogeneity and identifies prognostic biomarkers for immunotherapy in non-small cell lung cancer.","authors":"Jianye Yuan, Zelin Weng, Zhenguo Li, Rui Chen, Chao Cheng, Weixiong Yang, Xiuying Xie, Chang Luo, Tao Wang, Shuishen Zhang, Zihui Tan","doi":"10.1007/s00262-026-04454-4","DOIUrl":"10.1007/s00262-026-04454-4","url":null,"abstract":"<p><strong>Background: </strong>Gene-wise intratumor heterogeneity (ITH), defined as spatial variability in the expression of individual genes across tumor regions, remains incompletely characterized in non-small cell lung cancer (NSCLC). Identifying low-ITH genes as predictive biomarkers offers a promising strategy to enhance the reliability of immunotherapy outcome prediction.</p><p><strong>Methods: </strong>We profiled gene-wise ITH using multi-region scRNA-seq data and a computational framework combining variance and clustering metrics. Prognostic low-ITH genes were screened via immunotherapy RNA-seq datasets and six machine learning algorithms to construct the LITHrisk score. Transcriptomic profiling and in vitro experiments elucidated the biological and functional relevance of key score components.</p><p><strong>Results: </strong>The gene-wise ITH landscape in NSCLC was delineated, with several critical immune checkpoint genes, including PD-L1, LAG3, and TIM-3, being identified as low-ITH genes. A low-ITH-derived signature, the LITHrisk score (PD-L1, CDK11B, CXCL13, RPS4Y1, AKR1B10, CRLF1), effectively predicted immunotherapy prognosis and response in NSCLC and other cancers. Tumors with a low LITHrisk score were characterized by enrichment of immune response-related pathways and heightened infiltration of immune cells, such as T cells, B cells, and myeloid cells. Furthermore, we found that component genes of the score were linked to key tumor characteristics: AKR1B10 was associated with tumor immune interactions, functioning via SPP1 regulation to suppress anti-tumor immunity, while CRLF1 was implicated in promoting a fibroblast-enriched microenvironment and modulating tumor cell motility.</p><p><strong>Conclusion: </strong>Our study provides a practical transcriptome-based tool for advancing precision immunotherapy and nominates potential therapeutic targets for enhancing treatment efficacy.</p>","PeriodicalId":520581,"journal":{"name":"Cancer immunology, immunotherapy : CII","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13578180/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148298683","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of PD-1⁺Tim-3⁺CD8⁺ T cells in pretreatment tumors on chemotherapy responses in esophageal cancer.","authors":"Tomoko Sumimoto, Kei Yamamoto, Takuro Saito, Shinya Urakawa, Tomohira Takeoka, Tomoki Makino, Yukinori Kurokawa, Atsunari Kawashima, Azumi Ueyama, Hidetoshi Eguchi, Yuichiro Doki, Hisashi Wada","doi":"10.1007/s00262-026-04303-4","DOIUrl":"https://doi.org/10.1007/s00262-026-04303-4","url":null,"abstract":"<p><p>While chemotherapy has traditionally been recognized for its direct cytotoxic effects on cancer cells, increasing attention has been directed towards its capability to modulate tumor immune mechanisms. However, the majority of studies have focused on the quantitative assessment of tumor-infiltrating lymphocytes (TILs), without evaluating their functional status. Therefore, the present study investigated the pre-therapeutic exhaustion status of TILs and its impact on the efficacy of neoadjuvant chemotherapy (NAC) in patients with esophageal squamous cell carcinoma (ESCC). TILs were isolated from 60 endoscopic biopsy samples from ESCC patients before NAC. The proportion of CD8⁺ TILs co-expressing PD-1 and Tim-3 was evaluated using flow cytometry. Their functional status was assessed by examining the expression of exhaustion markers (TOX, LAG-3, CD39), cytotoxic molecules (granzyme B, perforin), and cytokines (IFN-γ, TNF-α). A cytotoxic assay was also performed to evaluate their direct killing capacity against anti-CD3scFv BALL-1 cells. A high proportion of PD-1⁺Tim-3⁺CD8⁺ TILs was significantly associated with a poor pathological response to NAC (p = 0.027) and was identified as an independent predictor of poor response in multivariate analysis (odds ratio = 4.1, 95% confidence interval = 1.1-14.7, p = 0.032). A functional analysis revealed that PD-1⁺Tim-3⁺CD8⁺ TILs expressed high levels of exhaustion markers and low levels of cytotoxic molecules and cytokines and also exhibited impaired cytotoxic function. The proportion of PD-1⁺Tim-3⁺CD8⁺ TILs decreased after NAC in responders. These results suggest the potential of a high proportion of PD-1⁺Tim-3⁺CD8⁺ TILs in the pre-treatment tumor microenvironment as a useful predictor of a poor NAC response in ESCC patients.</p>","PeriodicalId":520581,"journal":{"name":"Cancer immunology, immunotherapy : CII","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148274420","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A phase I study evaluating subcutaneous administration of the monoclonal antibody programmed cell death protein-1 (PD-1) inhibitor cetrelimab (JNJ-63723283) in patients with advanced solid malignancies.","authors":"Piotr Rutkowski, Dariusz M Kowalski, Victor Moreno, Aitana Calvo, Fiona Thistlethwaite, Ruth Plummer, Douglas Steinbach, John Loffredo, Sydney Akapeme, Daniel Jonathan, Vinod Philip, Angela Girvin, Shalaka Hampras, Peter Hellemans, Iurie Bulat","doi":"10.1007/s00262-026-04457-1","DOIUrl":"10.1007/s00262-026-04457-1","url":null,"abstract":"<p><strong>Purpose: </strong>Pharmacokinetics, pharmacodynamics, safety, and efficacy of subcutaneous cetrelimab were assessed in Parts (P)3 and 4 of the phase I LUC1001 study in patients with advanced/refractory solid tumors who progressed on or wereineligible for standard treatment and had no prior PD-1/PD-L1/PD-L2 treatment.</p><p><strong>Methods: </strong>In P3, low-concentration cetrelimab (30 mg/mL) was administered subcutaneously at 600 mg with a 6-week interval between doses 1 and 2, then every 3 weeks (Q3W). Based on P3 pharmacokinetic and safety findings, high-concentration cetrelimab (150 mg/mL) was administered subcutaneously at a 900 mg loading dose followed by 600 mg Q3W in P4.</p><p><strong>Results: </strong>Among 30 enrolled patients (P3, n = 11; P4, n = 19), median age was 54.5y; 76.7% received ≥ 3 prior lines of therapy. Median duration of treatment was 2.1mo. Treatment-related adverse events (AEs) occurred in 70% of patients, including 23.3% with grade ≥ 3 treatment-related AEs and 30.0% immune-related AEs; no treatment-related serious AEs or systemic infusion-related reactions occurred. After 3.7mo median follow-up, 2 patients (6.7%) achieved durable responses and 4 patients (13.3%) had stable disease for ≥ 24 weeks. Pharmacokinetic data showed that adding a 900 mg loading dose to the 600 mg Q3W subcutaneous regimen shortened the time to reach target recommended phase 2 dose (RP2D) exposures, making it a suitable intravenous alternative. Maximum PD-1 receptor occupancy was achieved with both formulations. Anti-cetrelimab antibodies were detected in 4 patients (13.3%); none were neutralizing.</p><p><strong>Conclusions: </strong>RP2D of subcutaneous cetrelimab was established as a loading dose of 900 mg followed by 600 mg Q3W. Subcutaneous cetrelimab demonstrated characteristics consistent with prior characterization of intravenous cetrelimab. Trial registration NCT02908906 at ClinicalTrials.gov, September 21, 2016; EudraCT 2016-002,017-22 at clinicaltrialsregister.eu, Jan 11, 2017.</p>","PeriodicalId":520581,"journal":{"name":"Cancer immunology, immunotherapy : CII","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13522328/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148274370","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bintrafusp alfa for patients with recurrent or metastatic olfactory neuroblastoma.","authors":"Nyall R London, Dara Bracken-Clarke, Elisabetta Xue, Isaac Brownell, Wojciech K Mydlarz, Evrim B Turkbey, Lisa M Cordes, Jennifer L Marté, Lisa M Rooper, Shrey B Shah, Michell Manu, Zoukaa B Sargi, James L Gulley, Charalampos S Floudas","doi":"10.1007/s00262-026-04462-4","DOIUrl":"10.1007/s00262-026-04462-4","url":null,"abstract":"<p><strong>Background: </strong>There is no established treatment for patients with recurrent/metastatic (R/M) olfactory neuroblastoma (ONB), a rare sinonasal tumor. We conducted the first immunotherapy clinical trial (NCT05012098) in patients with R/M ONB, to evaluate the activity of the bifunctional TGF-β \"trap\"/anti-PD-L1 fusion protein bintrafusp alfa (BA).</p><p><strong>Methods: </strong>Patients received BA (1200 mg, intravenously) every 2 weeks. Primary endpoint was overall response rate (ORR); secondary objectives included safety, progression-free survival (PFS), and overall survival (OS).</p><p><strong>Results: </strong>Between June 2022 and June 2023, 11 patients received treatment (Cohort 1, no prior immunotherapy, n=9; Cohort 2, prior immunotherapy received, n=2); enrollment was stopped due to BA development discontinuation. No objective responses were observed. In Cohort 1, 4 patients (of 8 evaluable, 50%) had stable disease (SD), three confirmed and long lasting; median PFS was 3.7 months, median OS was not reached; and one of SD patients had a complete metabolic response on ⁶⁸Ga-DOTATATE imaging. In Cohort 2, 1 patient had SD; median PFS was 3 months, and median OS was 6.8 months. Grade 3/4 treatment-related adverse events occurred in 3 patients (immune-mediated diabetes, esophageal hemorrhage, anemia, epistaxis).</p><p><strong>Conclusions: </strong>Although the primary endpoint was not met, BA showed a manageable safety profile and a subset of patients derived clinical benefit with prolonged stable disease, including one patient with a complete metabolic response. This first clinical trial of systemic therapy in R/M ONB serves as proof of clinical trials feasibility in this setting and supports further investigation of combinatorial immunotherapy strategies in this patient population. Trial registration ClinicalTrials.gov Identifier: NCT05012098, https://clinicaltrials.gov/ct2/show/NCT05012098 . Registered 18 August 2021.</p>","PeriodicalId":520581,"journal":{"name":"Cancer immunology, immunotherapy : CII","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13522318/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148267972","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CXCL9/SPP1-polarized tumor-associated macrophages exert dual roles in regulating anti-tumor immunity in lung adenocarcinoma.","authors":"Haixiao Liu, Lingyun Wang, Changlin Li, Dongtao Li, Linghan Meng, Guangda Zheng, Juanxia Ren, Lu Shang, Yanju Bao","doi":"10.1007/s00262-026-04456-2","DOIUrl":"10.1007/s00262-026-04456-2","url":null,"abstract":"<p><strong>Background: </strong>CS polarity, the mutually exclusive expression of CXCL9 and SPP1, is a key feature of tumor-associated macrophages (TAMs) in the lung adenocarcinoma (LUAD) microenvironment. The mechanisms and impact of CS polarity on tumor progression remain incompletely understood. The study aims to define the molecular basis of CS polarity and its role in LUAD progression to inform new immunotherapies.</p><p><strong>Methods: </strong>Single-cell RNA sequencing was used to characterize TAM subsets within the LUAD microenvironment, with survival analysis assessing their prognostic values and CellChat mapping cell-cell communication. In the functional validation section, a CS polarization regulation model of THP-1 cells was established. The Transwell co-culture system was utilized to evaluate its effects on the malignant behaviors of LUAD cells. CCK-8 assay, colony formation assay and cell migration assay were performed to detect cell proliferation and metastatic capacities. Flow cytometry was applied to determine the polarized phenotypes of TAMs (CD86⁺/CD163⁺). Dual-luciferase reporter assay was conducted to verify the direct transcriptional regulation of HPGDS promoter by MEF2C. Western blot, immunocytochemistry and qRT-PCR were adopted to analyze the activity of key signaling pathways. Furthermore, the above findings were further validated in vivo using a subcutaneous transplantation tumor model in nude mice.</p><p><strong>Results: </strong>Five functionally distinct TAM subsets were identified. SPP1⁻CXCL9^high TAMs were enriched in immune-activation pathways and strongly associated with favorable LUAD prognosis, whereas SPP1⁺CXCL9^low TAMs participated in immune suppression and tumor-promoting processes, correlating with poor outcome. In vitro, increasing the CXCL9/SPP1 ratio synergistically promoted macrophages toward an M1 phenotype and suppressed LUAD cell proliferation, migration and invasion. In addition, CS polarity reversal further promoted MEF2C nuclear translocation and HPGDS transcription by activating the p38/MAPK signaling axis. Dual-luciferase reporter assays directly confirmed that MEF2C activated HPGDS transcription via specifically binding to its promoter, which served as a critical molecular event that induced phenotypic switching of TAMs and triggered their antitumor functions. In vivo experiments using the subcutaneous transplantation tumor model in nude mice further verified that combined treatment with KO-SPP1 and OE-CXCL9 markedly inhibited tumor growth and facilitated the polarization of intratumoral macrophages toward an antitumor phenotype, which was highly consistent with the in vitro findings.</p><p><strong>Conclusion: </strong>CS polarity modulates TAM polarization and their anti-tumor function through the p38/MAPK-MEF2C-HPGDS axis, offering theoretical foundation and potential targets for macrophage reprogramming-based LUAD immunotherapy.</p>","PeriodicalId":520581,"journal":{"name":"Cancer immunology, immunotherapy : CII","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13522294/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148261352","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"BAP1 loss impairs IFN-γ signaling and enhances NK cell-mediated cytotoxicity in myeloid leukemia.","authors":"Chiara Badami, Erna Islamagic, Linnea Blomén, Frida Svensson, Theebiga Kathirkamanathan, Kristoffer Hellstrand, Elin Bernson, Fredrik B Thorén","doi":"10.1007/s00262-026-04453-5","DOIUrl":"10.1007/s00262-026-04453-5","url":null,"abstract":"<p><p>Natural killer (NK) cells recognize and eliminate malignant cells through multiple receptor-ligand interactions. To uncover genetic determinants of the susceptibility of myeloid leukemia cells to NK cell cytotoxicity, we analyzed several genome-wide CRISPR screens. Among recurrent hits, the BRCA1-associated protein 1 (BAP1) gene emerged as a key factor protecting K562 leukemic cells from NK cell-mediated killing. Using BAP1 knockout (KO) models, we found that loss of BAP1 alone did not alter NK cell sensitivity. However, upon interferon-γ (IFN-γ) stimulation, BAP1 KO K562 cells exhibited reduced HLA class I induction, triggered enhanced NK cell degranulation, and showed increased sensitivity to NK cell-mediated cytotoxicity compared with wild-type cells. Further experiments revealed that BAP1-deficient cells displayed reduced expression of the IFN-γ receptor 1 (IFN-γ-R1). BAP1 knockdown across multiple myeloid leukemia cell lines selectively decreased HLA-E and IFN-γ-R1 expression in ASXL1-mutant backgrounds. These findings suggest that BAP1 may contribute to the regulation of IFN-γ responsiveness and immune evasion in myeloid leukemia.</p>","PeriodicalId":520581,"journal":{"name":"Cancer immunology, immunotherapy : CII","volume":"75 6","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13269568/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148255502","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Real-world outcomes of ipilimumab plus nivolumab in esophageal squamous cell carcinoma: a multi-institutional large cohort study.","authors":"Shuichiro Hara, Tomoki Makino, Shigeto Nakai, Kota Momose, Kotaro Yamashita, Koji Tanaka, Taro Satoh, Keijiro Sugimura, Ryohei Kawabata, Atsushi Takeno, Masaaki Motoori, Makoto Yamasaki, Hiroshi Miyata, Yutaka Kimura, Takushi Yasuda, Hidetoshi Eguchi, Yuichiro Doki","doi":"10.1007/s00262-026-04451-7","DOIUrl":"10.1007/s00262-026-04451-7","url":null,"abstract":"<p><strong>Background: </strong>Combination immune checkpoint inhibition with ipilimumab plus nivolumab (NIVO + IPI) has shown promising efficacy in advanced esophageal squamous cell carcinoma (ESCC) in the CheckMate648 trial. However, real-world evidence regarding its safety, efficacy as first-line therapy, and host-related biomarkers relevant to immunotherapy remains limited.</p><p><strong>Methods: </strong>This multicenter retrospective study evaluated a large cohort of 111 patients with unresectable advanced or recurrent ESCC who received first-line NIVO + IPI therapy. Treatment response, treatment-related adverse events, and prognostic factors were analyzed.</p><p><strong>Results: </strong>The objective response and disease control rates in cases with target lesions were 44.0% and 70.7%, respectively. Treatment-related adverse events ≥ Grade 2 occurred in 58 (52.3%) patients, including one Grade 4 event (type 1 diabetes) and two Grade 5 events (biliary infection and myocarditis). The median overall survival (OS) and progression-free survival were 22 months (95% confidence interval [CI]: 13-not reached) and 5 months (95% CI 3-8), respectively. OS was significantly affected by lymph node metastasis in unresectable advanced disease and by liver metastasis in recurrent disease. Multivariate analysis of OS identified the C-reactive protein-to-albumin ratio (CAR), a marker of host immune-inflammatory status, as the only independent prognostic parameter (hazard ratio = 2.99, 95% CI 1.35-6.63, P = 0.0071).</p><p><strong>Conclusions: </strong>In this large real-world cohort, first-line NIVO + IPI therapy demonstrated meaningful clinical activity and an acceptable safety profile in advanced ESCC. Treatment outcomes varied according to metastatic patterns, suggesting an influence of organ-specific immune microenvironments, and CAR emerged as a simple and robust prognostic biomarker. These findings support the real-world applicability of dual immune checkpoint blockade and highlight the importance of host immune context in patient selection.</p>","PeriodicalId":520581,"journal":{"name":"Cancer immunology, immunotherapy : CII","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13493756/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148255462","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Surufatinib plus toripalimab for patients with advanced solid tumors and disease progression after prior immunotherapy: an open-label multi-cohort phase 2 trial.","authors":"Panpan Zhang, Ming Lu, Lijie Song, Yanqiao Zhang, Zhendong Chen, Chunjiao Wu, Zhiping Li, Xing Zhang, Qian Xu, Jinghong Zhou, Haiyan Shi, Panfeng Tan, Songhua Fan, Weiguo Su, Lin Shen","doi":"10.1007/s00262-026-04419-7","DOIUrl":"10.1007/s00262-026-04419-7","url":null,"abstract":"<p><strong>Background: </strong>Immune checkpoint inhibitor (ICI) plus an anti-angiogenic agent has shown antitumor activity in patients whose disease had progressed on a prior ICI but further evidence across tumor types is needed.</p><p><strong>Methods: </strong>This phase 2 trial evaluated the efficacy and safety of surufatinib (anti-angiogenic multi-tyrosine-kinase inhibitor, 250 mg orally, once daily) plus toripalimab (programmed-death-1 [PD-1] inhibitor, 240 mg intravenously, once every three weeks) in adult patients with advanced solid tumors and progression on a PD-1/programmed death ligand 1 inhibitor. The primary endpoint was investigator-assessed objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.</p><p><strong>Results: </strong>A total of 28 patients were enrolled and received treatment. Two of 27 evaluable patients achieved partial response, for an ORR of 7.4% (95% CI: 0.9-24.3); the disease control rate was 66.7% (95% CI: 46.0-83.5). Median progression-free survival was 3.9 months (95% CI: 1.4-4.2) and overall survival was 13.0 months (95% CI: 8.6-21.6; median follow-up: 20.9 months). Efficacy findings were consistent when assessed per immune-related RECIST. Eleven (39.3%) patients experienced grade ≥ 3 treatment-related adverse events (TRAEs), most frequently increased blood pressure (n = 3, 10.7%) and liver damage (n = 2, 7.1%). TRAEs led to surufatinib discontinuation in two (7.1%) patients. There were no treatment-related deaths.</p><p><strong>Conclusions: </strong>ICI-based combination rechallenge with surufatinib-toripalimab conferred signal-generating activity in patients with advanced solid tumors, with a manageable safety profile. Studies in larger populations are warranted.</p>","PeriodicalId":520581,"journal":{"name":"Cancer immunology, immunotherapy : CII","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13490337/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148255475","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Donor-specific toxicity of copanlisib identified using immune-humanized mice.","authors":"Robyn E Becker, Jenny Résiliac, Kathleen L Gabrielson, Zhuoming Liu, Kristina E Howard","doi":"10.1007/s00262-026-04398-9","DOIUrl":"10.1007/s00262-026-04398-9","url":null,"abstract":"<p><p>Copanlisib is a pan-phosphoinositide-3-kinase-inhibitor originally indicated for adult patients with relapsed follicular lymphoma who had received at least two prior systemic therapies. At the time this study was conducted, it was approved for use by the FDA and was being evaluated in clinical trials in combination therapy with checkpoint inhibitors for a range of cancers.Prior to conducting studies with the combination of copanlisib and checkpoint inhibitors, we conducted a pilot study to determine route of administration, identify an appropriate dose, and assess the effects of copanlisib in bone marrow-liver-thymus (BLT) immune-humanized mice. We tested three doses of copanlisib via two routes of administration in humanized mice produced from three unique donors and evaluated tissue-based toxicity via histopathology and immune changes with flow cytometry.Histopathology showed no significant correlation in pathological findings based on copanlisib dose or administration route. However, analysis of the histopathology by donor revealed clear differences, with one donor showing significant pathology, regardless of treatment dose or route, while the other two donors showed little to no adverse treatment effects. Flow cytometric analysis showed the affected donor had significantly more activated T-cells present in the bone marrow regardless of dose or route of administration.Although our findings represent only one of three donors used in immune-humanized mice, this study suggests that some immune modulating therapeutic toxicity could be associated with specific genetic factors from individual patients rather than being dose related.</p>","PeriodicalId":520581,"journal":{"name":"Cancer immunology, immunotherapy : CII","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13490038/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148230511","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neoadjuvant immunochemotherapy followed by definitive radiotherapy in locally advanced head and neck squamous cell carcinoma: two-year survival outcomes.","authors":"Yi Xu, Yang Meng, Lin Gui, Ye Zhang, Runye Wu, Xuesong Chen, Xiaodong Huang, Kai Wang, Yuan Qu, Yuchao Ma, Jianghu Zhang, Jingbo Wang, Junlin Yi","doi":"10.1007/s00262-026-04367-2","DOIUrl":"https://doi.org/10.1007/s00262-026-04367-2","url":null,"abstract":"<p><strong>Purpose: </strong>To evaluate the clinical response, survival outcomes, and organ-preservation potential in locally advanced head and neck squamous cell carcinoma (LA-HNSCC) patients treated with neoadjuvant immunochemotherapy (NIC) followed by definitive radiotherapy (DRT).</p><p><strong>Methods: </strong>We retrospectively reviewed patients with stage III-IVb HNSCC treated with NIC followed by DRT between 2021 and 2023. Tumor response was assessed after NIC and after completion of DRT according to RECIST 1.1. Overall survival (OS) and progression-free survival (PFS) were estimated using the Kaplan-Meier method. Toxicities were graded according to CTCAE 5.0 criteria.</p><p><strong>Results: </strong>A total of 74 patients were included, with hypopharyngeal tumors accounting for 47.3%. All patients completed at least two cycles of NIC. After NIC, the objective response rate was 89.2%, with clinical complete response (cCR) and clinical partial response (cPR) rates of 1.4% and 87.8%, respectively. After DRT, the corresponding rates shifted to 17.6% and 77.0%, respectively. With a median follow-up of 24 months (range: 5-38 months), the estimated 2-year OS and PFS rates were 83.2% and 61.7%. Among patients with laryngeal or hypopharyngeal carcinoma, the larynx-preservation rate was 95.2% and the 2-year larynx-preservation OS reached 73.6%. NIC-related adverse events were predominantly grades 1-3 (90.0%).</p><p><strong>Conclusion: </strong>NIC followed by DRT was associated with high response rates, encouraging survival outcomes, and manageable toxicities in this retrospective cohort. While organ-preservation rates are promising, the modest PFS highlights the need for further investigation in larger or selective cohorts.</p>","PeriodicalId":520581,"journal":{"name":"Cancer immunology, immunotherapy : CII","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148230528","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}