Cancer immunology, immunotherapy : CII最新文献

{"title":"Dissecting response to neoadjuvant immunotherapy-treated melanoma using cancer-immunity cycle-associated signatures.","authors":"S C M A Wijnen, P Dimitriadis, I L M Reijers, A M Menzies, G V Long, L F A Wessels, C U Blank","doi":"10.1007/s00262-025-04094-0","DOIUrl":"10.1007/s00262-025-04094-0","url":null,"abstract":"<p><p>Neoadjuvant combination therapy with anti-PD-1 and anti-CTLA4 agents has significantly improved long-term survival in patients with metastatic melanoma, yet not all patients respond to treatment. Responders often exhibit upregulated baseline inflammatory signatures; however, these markers capture only a single facet of the Cancer-Immunity Cycle-a comprehensive model describing the sequential steps required for effective anti-cancer immunity. To determine whether non-responsiveness to immunotherapy arises from single or multiple 'defective' steps, we analyzed in melanoma patients, treated with neoadjuvant immunotherapy, gene signatures representing each step of the cycle. Patients not achieving a major pathological response showed overall lower expression of these signatures. Among the 'immune-hot' patients, we identified a low response subgroup defective in one step ('homing-to-the-tumor,' involving CXCL9 and CXCL10), making this a promising target for improving their outcomes.</p>","PeriodicalId":520581,"journal":{"name":"Cancer immunology, immunotherapy : CII","volume":"74 8","pages":"253"},"PeriodicalIF":5.1,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12198083/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144500252","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":"Neo-antigen specific cancer vaccines for acute lymphoblastic leukemia-challenges, opportunities, and future directions.","authors":"Victoria Bloch Blytt Sandstad, Signe Modvig, Morten Orebo Holmström","doi":"10.1007/s00262-025-04107-y","DOIUrl":"10.1007/s00262-025-04107-y","url":null,"abstract":"<p><p>Acute lymphoblastic leukemia (ALL) is the most common pediatric malignancy, with standard treatment consisting of intensive chemotherapy and corticosteroids. While curative in most cases, this regimen leads to significant toxicity and long-term sequelae. Recent advancements in cancer immunotherapy, including chimeric antigen receptor T cells and bispecific T cell engagers, have improved outcomes, yet are limited by toxicity and immune escape by target downregulation. Thus, novel less toxic treatment modalities are highly warranted. The tumor mutational burden in ALL is low, which results in a low number of potentially immunogenic neo-antigens that could be used as targets for neo-epitope-specific therapeutic cancer vaccines. However, recent findings in solid cancer demonstrate that it is not the quantity but the quality of neo-antigens in the tumor that determine the tumor-specific immune response. Furthermore, novel sequencing techniques such as long-read sequencing and optical genome mapping can identify unknown genetic aberrations that may be targeted by neo-antigen vaccines. In ALL, both the ETV6-RUNX1 and BCR-ABL1 fusion genes, and the RAS-isoform mutations are frequent, and these genomic alterations generate immunogenic neo-epitopes. Additionally, therapeutic cancer vaccinations are well suited for ALL as the tumor burden is extremely low at time of a potential post-induction vaccination therapy, and patients are relatively young and are therefore less affected by immunosenescence. Thus, we envisage that neo-antigen specific therapeutic cancer vaccines could pose an important modality in future treatment algorithms for ALL.</p>","PeriodicalId":520581,"journal":{"name":"Cancer immunology, immunotherapy : CII","volume":"74 8","pages":"248"},"PeriodicalIF":5.1,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12185831/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144478535","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":"Cell-specific nanoengineering strategy to disrupt tolerogenic signaling from myeloid-derived suppressor cells and invigorate antitumor immunity in pancreatic cancer.","authors":"Nilesh U Deshpande, Anna Bianchi, Haleh Amirian, Iago De Castro Silva, Christine I Rafie, Bapurao Surnar, Karthik Rajkumar, Akash Ashokan, Ifeanyichukwu C Ogobuiro, Manan Patel, Erietta Stelekati, Shanta Dhar, Jashodeep Datta","doi":"10.1007/s00262-025-04096-y","DOIUrl":"10.1007/s00262-025-04096-y","url":null,"abstract":"<p><p>Pancreatic ductal adenocarcinoma (PDAC) is characterized by intratumoral abundance of neutrophilic/polymorphonuclear myeloid-derived suppressor cells (PMN-MDSC) which exert anti-T-cell functions through multiple mechanisms, especially JAK2/STAT3-regulated arginase activity. To overcome limitations of systemic inhibition of PMN-MDSCs in cancer-bearing patients such as neutropenia and compensatory myelopoietic adaptations, we developed a nanoengineering strategy to disrupt cell-specific signaling exclusively in PMN-MDSCs without compromising viability or provoking neutropenia. Single-cell RNA sequencing in human/murine PDAC, and flow cytometry in peripheral blood cells from treatment-naïve PDAC patients, nominated surface receptor CXCR2 as a PMN-MDSC-exclusive target. We chemically modified a small-molecule CXCR2 inhibitor AZD5069 by conjugating it with polyethylene glycol (PEG) to enhance aqueous solubility. This AZD5069-PEG construct was then chemically grafted onto amphiphilic polysaccharide derivatives to engineer CXCR2-homing nanoparticles (CXCR2-NP). Cy5.5 dye-loaded CXCR2-NPs showed near-exclusive uptake in PMN-MDSCs compared with Kras^LSL.G12D/+;p53^R172H/+;Pdx1^Cre/+ (KPC) PDAC tumor cells, KPC cancer-associated fibroblasts, macrophages, and dendritic cells. Encapsulation of JAK2/STAT3i Ruxolitinib (CXCR2-NP^Ruxo) resulted in more efficient and durable attenuation in STAT3-regulated arginase activity from PMN-MDSCs as well as robust induction of cytolytic T-cell activity compared with free Ruxolitinib in vitro and in orthotopic tumor cell-CAF co-injection models in vivo. Treatment of orthotopic tumor-bearing KPC mice with CXCR2-NP^Ruxo reduced tumor burden compared with vehicle, free Ruxolitinib, or non-drug-loaded CXCR2-NP treatments, without causing appreciable neutropenia. Taken together, cell-specific delivery of payloads via CXCR2-homing immunonanoparticles represents a novel strategy to disrupt MDSC-mediated immunosuppression and invigorate antitumor immunity in PDAC.</p>","PeriodicalId":520581,"journal":{"name":"Cancer immunology, immunotherapy : CII","volume":"74 8","pages":"247"},"PeriodicalIF":5.1,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12185796/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144478534","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":"Tertiary lymphoid structures in the microenvironment of colorectal cancer: exploring new therapeutic targets.","authors":"Nan-Nan Dai, Man-Yi Hu, Jian-Ping Wang, Zhi-Hui Dai, Li Xu, Tai-Wei Ye","doi":"10.1007/s00262-025-04108-x","DOIUrl":"10.1007/s00262-025-04108-x","url":null,"abstract":"<p><p>Immunotherapy has shown limited efficacy in colorectal cancer (CRC), necessitating the urgent identification of novel immunotherapeutic targets to address this challenge. Tertiary lymphoid structures (TLSs) are complex immune structures that spontaneously form within and outside of the tumor microenvironment, resembling secondary lymphoid organs. The formation of TLS formation dynamically adapts to the tumor microenvironment, with their immune function maintained by resident immune cells and cytokine networks. TLS develops antitumor immune competence following dynamic reorganization of their cellular components and proportions, although the precise mechanistic underpinnings remain to be fully characterized. Numerous studies have demonstrated that TLS can modulate the immune status of CRC, potentially enhancing the efficacy of immunotherapy. Currently, the clinical setting lacks appropriate immunological markers to assess immunotherapy outcomes, and TLS may offer a solution to this limitation. This article will review current research on TLS as a novel therapeutic target in the immunotherapy of malignant colorectal tumors.</p>","PeriodicalId":520581,"journal":{"name":"Cancer immunology, immunotherapy : CII","volume":"74 8","pages":"245"},"PeriodicalIF":5.1,"publicationDate":"2025-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12182536/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144340788","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":"Immunological synapse formation as a key mechanism in T cell-dependent bispecific antibody-mediated immune activation and cytotoxicity.","authors":"Rikuto Nakamura, Ryo Tsumura, Takahiro Anzai, Ryutaro Asano, Masahiro Yasunaga","doi":"10.1007/s00262-025-04036-w","DOIUrl":"10.1007/s00262-025-04036-w","url":null,"abstract":"<p><p>T cell-dependent bispecific antibodies (TDBs) are next-generation antibody therapies that link cancer cells and T cells to achieve potent antitumor effects. Despite the successful development of TDBs for hematological malignancies, their efficacy against solid tumors remains limited. Overcoming this challenge requires a deeper understanding of their mechanisms of action. While the basic process of immunological synapse (IS) formation and T cell activation by TDB is known, the detailed effects of IS on the bystander effect and T cell migration, both crucial for therapeutic efficacy, remain unclear. This study investigated these mechanisms using an EGFR/CD3 TDB (hEx3) and EGFR knockout cancer cells (KO). The results revealed that IS formation by TDB induced a bystander effect, leading to damage in surrounding KO, with the extent depending on the proportion of EGFR-positive wild-type cancer cells (WT) and the duration of co-culture. Furthermore, IS formation significantly enhanced T cell cytokine and chemokine secretion, promoting T cell migration. These findings provide critical insights into TDB efficacy mechanisms and highlight the importance of evaluating IS formation in developing new antibody drugs. Establishing a reliable system for assessing IS formation will be essential for advancing TDBs and other antibody-based therapies, particularly against solid tumors.</p>","PeriodicalId":520581,"journal":{"name":"Cancer immunology, immunotherapy : CII","volume":"74 8","pages":"246"},"PeriodicalIF":5.1,"publicationDate":"2025-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12182548/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144340787","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":"Clinical factors associated with growth and neoantigen reactivity of tumor infiltrating lymphocytes from metastatic epithelial cancers.","authors":"Alexandra M Gustafson, Aaron J Dinerman, Kyle J Hitscherich, Maria R Parkhurst, Hyunmi Halas, Donald E White, Chuong D Hoang, Jonathan M Hernandez, Mei Li M Kwong, Nicholas D Klemen, Steven A Rosenberg, Stephanie L Goff, James C Yang","doi":"10.1007/s00262-025-04091-3","DOIUrl":"10.1007/s00262-025-04091-3","url":null,"abstract":"<p><strong>Background: </strong>Adoptive cell therapy with tumor infiltrating lymphocytes is FDA approved for metastatic melanoma. TIL from patients with melanoma and factors relating to growth and reactivity have been studied; however, this has not been explored in patients with epithelial cancers.</p><p><strong>Patients and methods: </strong>Metastatic epithelial tumors resected for TIL growth from 2014 to 2023 were analyzed. Two hundred and ninety-one operations were performed to collect TIL for potential treatment. Of these, 263 harvests were each processed for up to 24 individual fragment cultures and screened for neoantigen recognition of the expressed products of cancer mutations. Patient and tumor characteristics were collected. Endpoints were growth (defined as more than half of all fragment cultures expanded for viable cryopreservation) and patient-specific neoantigen reactivity (release of interferon-γ in cocultures measured by ELISpot and 4-1BB upregulation on flow cytometry).</p><p><strong>Results: </strong>TIL fragments reached adequate growth for screening by 21 days. Metastatic resections from lung were more likely to grow TIL than all other resection sites combined (95%, p = 0.0011), while hepatic resections were less likely to grow (69%, p < 0.0001). One hundred and thirty-five patients (51%) had highly reactive TIL, 68 (26%) had weakly reactive TIL, and 60 (23%) had TIL with no neoantigen reactivity. Patients with prior exposure to immune checkpoint blockade therapy were less likely to have highly reactive TIL (p = 0.0325). Metastatic resection site impacted TIL reactivity against neoantigens, with those harvested from the lung more likely to show any reactivity (83%, p = 0.0180), as well as high reactivity (59%, p = 0.0066).</p><p><strong>Conclusions: </strong>Prior immune checkpoint therapies reduced the likelihood of having highly reactive TIL. Neoantigen reactivity was more common in TIL from thoracic resections versus other sites. Conversely, hepatic lesions yielded TIL less likely to grow and with less reactivity. These results contribute to improved strategies for sequencing TIL with other therapies and planning TIL harvests for patients with epithelial cancers.</p>","PeriodicalId":520581,"journal":{"name":"Cancer immunology, immunotherapy : CII","volume":"74 8","pages":"244"},"PeriodicalIF":5.1,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12179044/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144328341","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":"Extracellular vesicles derived from mature dendritic cells loaded with cDC1-specific chemokine XCL1 combined with chemotherapy-induced ICD for the treatment of castration-resistant prostate cancer.","authors":"Zhongqiang Fan, Zhao Wang, Hui Zhang, Hao Zhang, Rui Zhao, Shimiao Zhu, Xiaoqiang Liu","doi":"10.1007/s00262-025-04070-8","DOIUrl":"10.1007/s00262-025-04070-8","url":null,"abstract":"<p><strong>Background: </strong>Dendritic cells (DCs) derived extracellular vesicles represent a promising vehicle for the activation of adaptive immunity, demonstrating significant potential in the development of cancer nanovaccines. The aim of this study was to evaluate the antitumor efficacy of a functional DCs-derived extracellular vesicles in castration-resistant prostate cancer.</p><p><strong>Methods: </strong>A pre-modification strategy was employed to overexpress XCL1 in dendritic cells, enabling their extracellular vesicles to highly express XCL1 protein. In vitro experiments, prostate cancer-bearing mouse models, and OVA-expressing prostate cancer mouse models demonstrated that dendritic cells efficiently internalize extracellular vesicles derived from XCL1-overexpressing mature dendritic cells (DEX_XCL1), thereby enhancing the chemotaxis, activation, and antigen-presenting capacity of cDC1 cells. When combined with the immunogenic cell death effect induced by cisplatin, this approach significantly increased the number and cytotoxic activity of CD8⁺ T cells, improved the tumor microenvironment, and effectively suppressed prostate cancer tumor growth.</p><p><strong>Results: </strong>The coding sequence of XCL1 successfully inserted upstream of the PDGFR transmembrane domain and transfected into dendritic cells, enabling their extracellular vesicles to highly express XCL1 protein. Extracellular vesicles derived from XCL1-overexpressing mature dendritic cells not only exhibited high XCL1 expression, but were also enriched with chemokine receptor CCR7 and MHC I molecules on their surface. This nanovaccines enhanced the uptake of extracellular vesicles by dendritic cells, recruited cDC1 cells within the tumor tissue, and significantly improved their antigen-presenting capacity. When combined with the immunogenic cell death effect induced by cisplatin, which generates a large amount of tumor-associated antigen STEAP1, this strategy effectively enhanced the proliferation and cytotoxic activity of CD8⁺T cells. Moreover, it reduced the proportion of regulatory T cells and immunosuppressive factors, thereby reshaping the tumor immune microenvironment. This approach effectively inhibited tumor growth in mice and prolonged their survival. These findings demonstrate the strong synergistic effects of the nanovaccines and cisplatin in promoting antitumor immunity.</p><p><strong>Conclusions: </strong>A novel nanovaccines induces potent antitumor immune responses and, in combination with the chemotherapeutic agent cisplatin, effectively remodels the tumor immune microenvironment. This approach offers a new strategy and preclinical evidence for the immunotherapy of \"cold tumors\" prostate cancer.</p>","PeriodicalId":520581,"journal":{"name":"Cancer immunology, immunotherapy : CII","volume":"74 8","pages":"242"},"PeriodicalIF":5.1,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12176708/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144328342","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":"Clinical efficacy and biomarkers of neoadjuvant chemoimmunotherapy in locally advanced esophageal squamous cell carcinoma.","authors":"Siyou Deng, Qi Wang, Yueping Li, Ruijie Zhang, Jinjie Li, Yujie Zhang, Yixin Cai, Wei Sun, Jiang Chang, Ni Zhang, Li Zhang","doi":"10.1007/s00262-025-04099-9","DOIUrl":"10.1007/s00262-025-04099-9","url":null,"abstract":"<p><strong>Background: </strong>Neoadjuvant immunotherapy has emerged as a promising strategy for treating esophageal squamous cell carcinoma (ESCC). This study evaluates the therapeutic efficacy and safety of neoadjuvant immunochemotherapy (nICT) in ESCC and explores potential biomarkers associated with treatment outcomes.</p><p><strong>Methods: </strong>Patients with locally advanced ESCC were enrolled and received two cycles of nICT followed by surgical resection. The primary endpoint was the pathological complete response rate, while secondary endpoints included overall survival (OS), event-free survival (EFS), safety, and the identification of predictive biomarkers.</p><p><strong>Results: </strong>A total of 47 patients were enrolled in the study, with 42 undergoing surgical resection, all of whom achieved R0 resection. The rates of complete and partial pathological responses were 28.5% and 16.7%, respectively. The 1-year and 2-year EFS rates were 82% and 37.3%, while OS rates were 100% and 71.4%, respectively. The majority of treatment-related adverse events were Grade 1-2, and no surgical delays were observed. RNA sequencing analysis identified epithelial-mesenchymal transition as the most significantly enriched pathway in non-responders. Notably, higher infiltration of normal fibroblasts was associated with improved pathological response and enhanced long-term survival, while myofibroblastic cancer-associated fibroblasts (myCAF) negatively impacted treatment efficacy and clinical outcomes.</p><p><strong>Conclusions: </strong>Neoadjuvant PD-1 inhibitors combined with chemotherapy show promising potential for patients with locally advanced ESCC, inducing a robust immune response that correlates with clinical outcomes. The infiltration of myCAF emerges as a potential predictive biomarker for treatment response and disease progression, underscoring the need for further mechanistic exploration and validation in larger cohorts.</p>","PeriodicalId":520581,"journal":{"name":"Cancer immunology, immunotherapy : CII","volume":"74 8","pages":"243"},"PeriodicalIF":5.1,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12176704/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144328340","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":"Tislelizumab and GP regimen neoadjuvant therapy followed by concurrent chemoradiotherapy with nimotuzumab in patients with stage IVA nasopharyngeal carcinoma: a retrospective study.","authors":"Mingfen Lai, Shuai Li, Zhongwen Jin, Mingzhang Chang, Fangming Li, Peixin Yang, Yiming He, Qinhua Zhang","doi":"10.1007/s00262-025-04100-5","DOIUrl":"10.1007/s00262-025-04100-5","url":null,"abstract":"<p><strong>Objective: </strong>We aimed to retrospectively evaluate the safety and efficacy of tislelizumab combined with the gemcitabine and cisplatin (GP) regimen as neoadjuvant therapy followed by nimotuzumab with concurrent chemoradiotherapy (CCRT) for locoregionally advanced nasopharyngeal carcinoma (LANPC).</p><p><strong>Patients and methods: </strong>From March 2021 to January 2022, 44 patients were included in our hospital. Tislelizumab and the GP regimen were given every three weeks for 1-4 cycles, followed by nimotuzumab with chemoradiotherapy, which included lobaplatin and intensity-modulated radiation therapy (IMRT). All patients were analyzed for tumor response at regular intervals during induction therapy, chemoradiotherapy, and follow-up visits.</p><p><strong>Results: </strong>Forty-one (93%) patients completed 4 cycles of GP and tislelizumab during neoadjuvant treatment. Forty-one patients (93%) finished two cycles of lobaplatin treatment, and forty-two patients (95%) finished six weeks of nimotuzumab treatment during concurrent chemoradiotherapy. Of the patients, twenty (46%) had a complete response, and twenty-four (55%) had a partial response prior to CCRT. After chemoradiotherapy, 91% of patients (40 out of 44) and 98% of patients (43 out of 44) had complete responses, respectively, at three and six months. With 34 months of median follow-up time, overall survival and progression-free survival were not reached. The 2-year overall survival rate was 93% (95% CI, 0.803-0.977), and the 2-year progression-free survival rate was 91% (95% CI, 0.776-0.965). Of the patients, 43% had treatment-related adverse events, and 9.1% had immune-related adverse events (irAEs) from grades 3-4.</p><p><strong>Conclusion: </strong>Tislelizumab plus induction chemotherapy followed by nimotuzumab with chemoradiotherapy significantly improved tumor response, superior progression-free survival, and manageable safety for high-risk LANPC. However, our study demonstrates the potential benefits of combining nimotuzumab with chemoradiotherapy after neoadjuvant chemotherapy in high-risk LANPC patients; the findings are preliminary and must be validated by larger, more rigorously designed trials.</p>","PeriodicalId":520581,"journal":{"name":"Cancer immunology, immunotherapy : CII","volume":"74 8","pages":"241"},"PeriodicalIF":5.1,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12173978/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144319170","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":"NLRP3 activation promotes cGAS/STING signaling and antitumor immunity by colorectal cancer cells.","authors":"Courtney Mowat, Daniel Schiller, Kristi Baker","doi":"10.1007/s00262-025-04088-y","DOIUrl":"10.1007/s00262-025-04088-y","url":null,"abstract":"<p><strong>Introduction: </strong>Colorectal cancer (CRC) is a highly prevalent and deadly disease that is largely refractory to immunotherapy. The only CRC subset that responds to these therapies is characterized by prevalent microsatellite instability (MSI), extensive  CD8+ T cell infiltration and high expression of innate immune signaling pathways. Endogenous activation of the cGAS/STING pathway is essential for this CD8+ T cell antitumor response in MSI CRCs, suggesting that activating it in other CRCs could boost immunotherapy response rates. In contrast, activation of the NLRP3 inflammasome is typically associated with tumor-promoting inflammation although this has primarily been studied in immune cells.</p><p><strong>Methods: </strong>We used a mixture of flow cytometry, activation assays, in vivo orthotopic models and patient-derived organoids to investigate the effect of NLRP3 activation in CRC cells on cGAS/STING-mediated antitumor immunity.</p><p><strong>Results: </strong>Our results show that activation of the NLRP3 inflammasome specifically in CRC cells boosts cGAS/STING signaling in both MSI and non-MSI CRCs and that dual stimulation increases CD8+ T cell-mediated antitumor immunity. The ability of NLRP3 to enhance cGAS/STING signaling was specific and did not occur with activation of other innate immune pathways such as AIM2 or TLRs. Enhancement of cGAS/STING signaling by NLRP3 proceeded via a positive feedback loop that was inflammasome-independent and required early crosstalk between the signaling mediators and regulation of their gene expression.</p><p><strong>Conclusions: </strong>Activation of NLRP3 specifically in CRC cells could be a promising strategy to boost antitumor immunity in otherwise immunotherapy resistant CRCs.</p>","PeriodicalId":520581,"journal":{"name":"Cancer immunology, immunotherapy : CII","volume":"74 8","pages":"238"},"PeriodicalIF":5.1,"publicationDate":"2025-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12145389/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144251872","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}