Cancer immunology, immunotherapy : CII最新文献

{"title":"Neoadjuvant combined immunotherapy with intratumoral TransCon TLR7/8 Agonist and systemic TransCon IL-2 β/y or pembrolizumab in patients with locally advanced oral cancer-a monocentric experience.","authors":"Manuel Weber, Leah Trumet, Fabienne Lange, Julia Murk, Philipp Schubert, Hasan Alsamra, Joy Backhaus, Stefanie Corradini, Marco Kesting, Sarina Müller, Joan Morris, Marlen Haderlein","doi":"10.1007/s00262-026-04515-8","DOIUrl":"10.1007/s00262-026-04515-8","url":null,"abstract":"<p><strong>Purpose: </strong>Combination immunotherapy has shown encouraging activity across multiple solid tumors. We report the complete and consecutive cohort of patients with locally advanced oral squamous cell carcinoma (OSCC) treated at a single center within the prospective, multicenter, randomized phase 2 BelieveIT-201 trial (ASND0038), evaluating neoadjuvant intratumoral Toll-like receptor (TLR) 7/8 agonist (TransCon TLR7/8 Agonist) therapy combined with systemic immunotherapy.</p><p><strong>Methods: </strong>Patients with non-metastatic OSCC treated within the BelieveIT-201 trial (ASND0038) between April and December 2024 were included. Neoadjuvant therapy comprised two cycles of intratumoral TransCon TLR7/8 Agonist combined with either intravenous pembrolizumab or TransCon IL-2 β/γ according to 1:1 randomization, followed by surgical resection. The trial was terminated prematurely by the sponsor for reasons unrelated to safety or efficacy, which limited the cohort to six patients. Clinical, radiographic, pathological responses, and safety were assessed. Immunohistochemical analyses of paired pre- and post-treatment tumor samples evaluated immune cell infiltration (CD3, CD8, CD68, CD163). The individual patient was the unit of analysis, and given the small number of patients all analyses are descriptive; no inferential statistical testing was performed. Progression-free survival (PFS) and overall survival (OS) are reported as absolute event counts.</p><p><strong>Results: </strong>Six patients were treated (median age 63 years; median follow-up 81 weeks). Three patients achieved a major clinical response, two showed partial response, and one had progressive disease. Pathologic evaluation revealed one complete response, one major response, and four non-responses. All patients underwent surgery; postoperative morbidity was substantial, with at least one grade III adverse event in every patient and one postoperative death. All three patients with a major clinical response developed sterile tumor-associated pseudoabscesses in spatial proximity to the injection site. Immunohistochemical analyses revealed remodeling of the tumor immune microenvironment, including increased T-cell infiltration, most pronounced in the tumor center. Within the first year, two of six patients experienced a progression-free survival event (n = 1 progressive disease, n = 1 death). After surgery none of the patients showed disease recurrence.</p><p><strong>Conclusion: </strong>Neoadjuvant intratumoral TransCon TLR7/8 Agonist-based combination immunotherapy was feasible in this small prospective cohort of patients with locally advanced OSCC and was accompanied by consistent remodeling of the tumor immune microenvironment. Because of the limited number of patients and the premature termination of the parent trial, no conclusions on efficacy or on comparative tolerability can be drawn.</p>","PeriodicalId":520581,"journal":{"name":"Cancer immunology, immunotherapy : CII","volume":"75 10","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13554004/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148914933","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":"The effect and mechanism of TIPE in promoting M2 polarization through DcR3 in the microenvironment of colorectal cancer.","authors":"Shiying Zhang, Chunlin Shen, Zeyang Lin, Qiang Zhu, Yihan Feng, Liwei Sun, Chengjia Zhang, Haole Zhang, Lumin Wang, Shuyu Chen, Jiyi Huang, Yuhan Ye, Xingfeng Qiu, Guohong Zhuang","doi":"10.1007/s00262-026-04531-8","DOIUrl":"10.1007/s00262-026-04531-8","url":null,"abstract":"<p><strong>Background: </strong>Elevated expression of tumor necrosis factor α-induced protein 8 (TIPE) is observed in colorectal cancer (CRC) and is known to regulate decoy receptor 3 (DcR3) expression while promoting M2 polarization of macrophages. However, the precise role of DcR3 in macrophage M2 polarization remains to be elucidated.</p><p><strong>Methods: </strong>We employed bioinformatic analysis alongside in vitro and in vivo experimental approaches to investigate the regulatory mechanism by which TIPE influences macrophage M2 polarization in CRC.</p><p><strong>Results: </strong>TIPE expression in CRC tissues positively correlates with M2 macrophage markers (CD206, CD163, IL-10). Functionally, TIPE promotes M2 polarization of macrophages by upregulating DcR3. Mechanistically, DcR3 binds to heparan sulfate proteoglycan 2 (HSPG2) in a heparan sulfate (HS)-dependent manner, leading to activation of the protein kinase Bα1 (AKT1) signaling pathway. AKT1 activation not only directly drives M2 polarization but also enhances macrophage chemotaxis and recruitment toward CRC cells by upregulating the chemokine CXCL8.</p><p><strong>Conclusions: </strong>This study reveals a novel mechanism through which TIPE regulates M2 macrophage polarization and function via DcR3, offering new perspectives for the diagnosis and therapeutic targeting of CRC.</p>","PeriodicalId":520581,"journal":{"name":"Cancer immunology, immunotherapy : CII","volume":"75 10","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13601453/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149032855","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":"Correction: Haemostatic changes during CART cell therapy and risk of complications.","authors":"María Panizo-Inogés, María Marcos-Jubilar, Jose Ramón González-Porras, Carlos Puerta-Vazquez, Clara Fernández-Arias, Paula Rodríguez-Otero, Ana Alfonso-Pierola, Sara Villar, Miguel Ángel Canales, Josune Orbe, Jose Antonio Páramo, Felipe Prósper, Ramón Lecumberri","doi":"10.1007/s00262-026-04425-9","DOIUrl":"10.1007/s00262-026-04425-9","url":null,"abstract":"","PeriodicalId":520581,"journal":{"name":"Cancer immunology, immunotherapy : CII","volume":"75 9","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13506997/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148820645","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":"Correction: Dual-modality imaging enables longitudinal biodistribution profiling of intracerebroventricular CAR-T therapy in orthotopic glioma.","authors":"Chunzhao Li, Peng Zhang, Xiaobin Zhao, Rui Feng, Na Xian, Gangxiong Huang, Wenju Jiang, Zhenhua Hu, Yang Zhang, Nan Ji","doi":"10.1007/s00262-026-04501-0","DOIUrl":"https://doi.org/10.1007/s00262-026-04501-0","url":null,"abstract":"","PeriodicalId":520581,"journal":{"name":"Cancer immunology, immunotherapy : CII","volume":"75 9","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13490328/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148805268","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":"Correction: Novel recombinant protein PK5-Gal-3C enhances the anti-tumor activity of T cells via binding with TRPV2.","authors":"Guopeng Zhang, Wei Zhang, Xiaohuan Wei, Zhenyu Wang, Feitong Wang, Shishuo Sun, Haiheng Xu, Xiangye Liu, Qing Zhang, Xiaoge Gao","doi":"10.1007/s00262-026-04499-5","DOIUrl":"https://doi.org/10.1007/s00262-026-04499-5","url":null,"abstract":"","PeriodicalId":520581,"journal":{"name":"Cancer immunology, immunotherapy : CII","volume":"75 9","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13490326/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148805276","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":"The CREM-IL-15 axis: decoding the persistence-exhaustion paradox in NK cell immunotherapy.","authors":"Amr Ali Mohamed Abdelgawwad El-Sehrawy, Mutaz Jamal Al-Khreisat, Jalpa R Patel, Makhfirat Kibriyeva, Lutfullayeva Gulnoza, Khayriddin Qosimov, Lhyb Mohammed Abdul, Navin Kumar Tailor","doi":"10.1007/s00262-026-04506-9","DOIUrl":"10.1007/s00262-026-04506-9","url":null,"abstract":"<p><p>Natural killer (NK) cells are critical components of the innate immune system, renowned for their ability to recognize and eliminate malignant and infected cells without prior sensitization. NK cell immunotherapy encompasses various approaches, including adoptive transfer of ex vivo expanded NK cells, cytokine stimulation to enhance their activity, and genetic modifications to improve persistence and specificity. CREM is a cAMP-responsive transcription factor that modulates gene expression in response to receptor- and cytokine-driven signaling. Recent evidence now shows that IL-15 and CAR stimulation rapidly induce CREM in activated NK cells. Rafei (Nature 643:1076-1086, 2025) further demonstrated in CAR-NK models that CREM functions as a regulatory checkpoint limiting NK cell cytotoxicity and cytokine production, while its relevance in resting/native NK cells remains to be established. The CREM-IL-15 signaling axis has emerged as a pivotal regulator of NK cell biology, influencing their development, activation, and longevity. IL-15 is a critical cytokine for NK cell survival, proliferation, and functional maturation. Understanding this axis is vital, as it offers insights into mechanisms that sustain NK cell activity and those that lead to functional exhaustion, thereby informing strategies to enhance therapeutic efficacy. A central challenge in NK cell immunotherapy is balancing cellular persistence with functional exhaustion. Persistent NK cell activity is desirable for sustained tumor control; however, prolonged activation often results in cellular exhaustion characterized by diminished cytotoxicity and cytokine production. This paradox hampers the long-term success of NK cell-based treatments. The CREM-IL-15 axis plays a complex role in this dynamic, potentially promoting NK cell survival and persistence while also contributing to exhaustion under certain conditions. Deciphering the molecular underpinnings of this paradox is essential for developing interventions that maintain NK cell functionality over time, thereby improving therapeutic outcomes in cancer patients.</p>","PeriodicalId":520581,"journal":{"name":"Cancer immunology, immunotherapy : CII","volume":"75 8","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13437876/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148671775","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":"Correction: Immunological impact of tumor-draining lymph node dissection on systemic Th1-like CD4⁺ T cells in patients with early-stage lung cancer.","authors":"Atsushi Kamigaichi, Hiroshi Kagamu, Yoshihiro Miyata, Takahiro Mimae, Norifumi Tsubokawa, Koichi Hirano, Morihito Okada","doi":"10.1007/s00262-026-04490-0","DOIUrl":"10.1007/s00262-026-04490-0","url":null,"abstract":"","PeriodicalId":520581,"journal":{"name":"Cancer immunology, immunotherapy : CII","volume":"75 8","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13428725/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148655589","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 neck nodal yield on immune checkpoint inhibitor outcome after recurrence in head and neck squamous cell carcinoma.","authors":"Dong Hyun Kim, Jiwon Koh, Yoon Kyung Jeon, Kyeong Cheon Jung, Jungirl Seok, Eun-Jae Chung, Seong-Keun Kwon, Soon-Hyun Ahn, Bhumsuk Keam","doi":"10.1007/s00262-026-04504-x","DOIUrl":"https://doi.org/10.1007/s00262-026-04504-x","url":null,"abstract":"<p><strong>Introduction: </strong>Neck dissection and adequate lymph node yield (LNY) are important in the treatment of head and neck squamous cell carcinoma (HNSCC). Cervical lymph nodes represent the primary sites for T-cell priming; however, the impact of LNY on the efficacy of immune checkpoint inhibitors (ICIs) remains unclear.</p><p><strong>Methods: </strong>A total of 120 patients with HNSCC who relapsed after surgical resection and subsequently received ICIs were included. The association of LNY, neutrophil-lymphocyte ratio (NLR), and programmed death-ligand 1 (PD-L1) expression with ICI outcomes were evaluated.</p><p><strong>Results: </strong>Among 120 patients, 31 underwent unilateral, 82 bilateral, and 7 no neck dissection. The median LNY was 26 (mean, 29.9; range, 0-145). PD-L1 expression was evaluated in 80 patients, 69 of whom had combined positive score ≥ 1. The low-LNY group had a higher overall response rate to ICI than the high-LNY group (42.9% vs. 16.9%, P = 0.003). Patients with high LNY had inferior PFS (median, 1.3 vs. 5.9 months; P < 0.001) and OS (median, 9.7 vs. 21.1 months; P = 0.007) compared with those with low LNY. In multivariable analysis, high LNY and high NLR were independent predictors of poor survival, whereas PD-L1 expression was not. Among patients with PD-L1-positive tumors, those with high NLR had inferior survivals compared with those with low NLR.</p><p><strong>Conclusions: </strong>Extensive lymphatic ablation, as reflected by high LNY, may be associated with diminished ICI efficacy in relapsed HNSCC. These findings suggest that LNY warrants further investigation as a potential biomarker for ICI outcomes in patients with post-surgical recurrent HNSCC.</p>","PeriodicalId":520581,"journal":{"name":"Cancer immunology, immunotherapy : CII","volume":"75 11","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149229775","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":"Dual inhibition of tumor cells and tumor-associated neutrophils by anti-CXCR2 antibodies suppresses tumor growth and augments immunotherapy efficacy in ARID1A-deficient pancreatic cancer.","authors":"Tzu-Lei Kuo, Kuan-Chung Hsiao, Ko-Jiunn Liu, Li-Tzong Chen, Wen-Chun Hung","doi":"10.1007/s00262-026-04498-6","DOIUrl":"10.1007/s00262-026-04498-6","url":null,"abstract":"<p><p>Pancreatic ductal adenocarcinoma (PDAC) is largely resistant to immune checkpoint blockade (ICB) due to its highly immunosuppressive tumor microenvironment. How to switch the \"immune-cold\" microenvironment to \"immune hot\" one is a clinical unmet need. We recently generated a genetically engineered PDAC mouse model (KAR) by combining K-Ras mutation and AT-rich interactive domain-containing protein 1A (ARID1A) inactivation in the pancreas. Compared to the KPC (K-Ras mutation + p53 inactivation) tumors, KAR tumors express higher C-X-C chemokine receptor 2 (CXCR2) and have more CXCR2⁺ neutrophils infiltration. Our previous study demonstrated that activation of CXCR2 by its cognate ligands promotes proliferation and drug resistance in PDAC cells. In addition, increase in tumor-associated neutrophils and high neutrophil-to-lymphocyte ratio are associated with worse prognosis in PDAC patients. Here, we developed a monoclonal antibody against human CXCR2 (huCXCR2-Ab) and tested its therapeutic effect in cells and in animals. Treatment with huCXCR2-Ab inhibited IL-8-induced downstream signaling, and the proliferation of human PDAC cancer cells. In addition, huCXCR2-Ab suppressed PDAC growth in an orthotopic nude mouse model. We next developed a monoclonal antibody against mouse CXCR2 (muCXCR2-Ab) and investigated its immune regulatory effect in vivo. We showed that muCXCR2-Ab reduced tumor burden, increased CD8⁺ T-cell infiltration, and decreased immunosuppressive neutrophils in the KAR mice. Moreover, muCXCR2-Ab augments the therapeutic efficacy of anti-PD-L1. Thus, dual targeting of CXCR2⁺ tumor cells and tumor-associated neutrophils remodels tumor microenvironment and enhances immunotherapy response in ARID1A-deficient PDAC, providing a new strategy for precision therapy of PDAC.</p>","PeriodicalId":520581,"journal":{"name":"Cancer immunology, immunotherapy : CII","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148537996","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":"Therapeutic targeting of CD47 using a tri-specific NK cell engager to inhibit multiple myeloma.","authors":"Ratchaneewan Sumankan, Prin Sungwan, Natthanich Boonsatit, Seiji Okada, Aussara Panya","doi":"10.1007/s00262-026-04431-x","DOIUrl":"10.1007/s00262-026-04431-x","url":null,"abstract":"<p><p>Multiple myeloma (MM), a hematological malignancy, remains an incurable disease due to the development of resistance to the treatment; thus, there is an urgent need for new and effective therapeutic strategies, particularly for patients who do not respond to standard therapies. High levels of Cluster of Differentiation 47 (CD47) expression have been reported in MM and are associated with disease progression. CD47 acts as a cancer immune escape mechanism by binding to SIRPα protein, resulting in inhibiting phagocytosis of macrophages and NK cell activity. Therefore, blocking the CD47 signaling pathway has emerged as a promising strategy for cancer immunotherapy. In this study, we confirmed that MM cells have high CD47 expression. We generated and characterized a tri-specific killer engager targeting CD47, namely TriKE-CD47, that targets both CD47 on MM cells and CD16 on NK cells. Additionally, it incorporates an IL-15 moiety to enhance NK cell proliferation. TriKE-CD47 treatment promoted a remarkable proliferation of NK cells overexpressing CD16 (N6 cells). Co-culturing MM cells with N6 cells, primary NK cells, and monocyte-derived macrophages in the presence of 200 ng of TriKE-CD47 significantly improved NK cytotoxicity and macrophage phagocyte activities against MM cells. Notably, the efficacy of TriKE-CD47 was directly correlated with CD47 expression levels on the target cells reflecting the specificity of TriKE-CD47 to target antigen. Furthermore, TriKE-CD47 effectively suppressed tumor growth in MM xenograft mice models. Taken together, these findings strongly supported that TriKE-CD47 could be a potential therapeutic for MM patients.</p>","PeriodicalId":520581,"journal":{"name":"Cancer immunology, immunotherapy : CII","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148521674","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}