Cancer Immunology, Immunotherapy最新文献

{"title":"Generation of frameshift-mutated TGFβR2-specific T cells in healthy subjects following administration with cancer vaccine candidate FMPV-1/GM-CSF in a phase 1 study.","authors":"Else Marit Inderberg, Nand Singh, Robert Miller, Sarah Arbe-Barnes, Henrik K Eriksen, Berit Lversen, Hedvig Vidarsdotter Juul, Jon Amund Eriksen, Karianne Risberg Handeland","doi":"10.1007/s00262-025-03969-6","DOIUrl":"10.1007/s00262-025-03969-6","url":null,"abstract":"<p><p>FMPV-1 is a component of FMPV-3, an investigational cancer-specific vaccine and being developed to activate anti-cancer T cell responses targeting frameshift mutations of MSI-H cancers. FMPV-1 is designed to activate T cell responses against transforming growth factor β receptor 2 (TGFβR2) frameshift mutation. Microsatellite instability high (MSI-H) gastrointestinal cancers frequently harbour TGFβR2 frameshift mutations. This first-in-human, phase 1, single centre, open-label study included 16 healthy male subjects who received FMPV-1 (0.15 mg/injection) plus granulocyte-macrophage colony-stimulating factor (GM-CSF) (0.03 mg/injection) as two separate, co-located, injections on Days 1, 8, 15, 29 and 43. All subjects were followed to Day 365. A FMPV-1-specific delayed type hypersensitivity (DTH) skin reactivity test was performed with FMPV-1 (without GM-CSF) on Days 1, 29 and 43 with assessment after 2 days. All subjects were DTH negative at baseline, 8/16 were positive on Day 31 and 15/16 were positive on Day 45. Furthermore, the FMPV-1/GM-CSF induced frameshift mutant TGFβR2-specific T cells after the short vaccination period, and specific T cells were still detectable after 6 and 12 months indicating induction of frameshift mutant TGFβR2-specific T memory cells. Adverse events were limited to mild injection site reactions with no evidence of related systemic signs or symptoms. No other clinically important changes to vital signs, electrocardiograms, haematological, coagulation or laboratory measures related to treatment were observed. FMPV-1/GM-CSF was well tolerated and generated vaccine-specific T cell immune responses in healthy subjects. These findings support clinical studies in patients with, or at risk of, cancers carrying TGFβR2 frameshift mutations.Clinical trial identification: ClinicalTrials.gov: NCT05238558. EudraCT: 2020-004363-80.</p>","PeriodicalId":9595,"journal":{"name":"Cancer Immunology, Immunotherapy","volume":"74 4","pages":"115"},"PeriodicalIF":4.6,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11861775/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143490779","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":"Microsatellite instability-high status as a pan-cancer biomarker for immunotherapy efficacy.","authors":"Thierry Landre, Gaëtan Des Guetz","doi":"10.1007/s00262-025-03980-x","DOIUrl":"10.1007/s00262-025-03980-x","url":null,"abstract":"<p><strong>Background: </strong>Microsatellite instability-high (MSI-H) cancers are linked to exceptional benefit from immune checkpoint inhibitors (ICIs), but studies on their efficacy across various MSI-H cancer types are limited.</p><p><strong>Methods: </strong>Randomized clinical trials (RCTs) comparing ICIs to chemotherapy in advanced MSI-H/dMMR cancers were systematically reviewed. Eligible studies included 13 RCTs with 1633 MSI-H patients across colorectal, gastric, and endometrial cancers. Data were analyzed using hazard ratios for progression-free survival (PFS) and overall survival (OS), with subgroup analyses by tumor type. Statistical heterogeneity was assessed using Cochrane's Q and I².</p><p><strong>Results: </strong>Immunotherapy significantly improved PFS and OS in MSI-H patients, with an HR for OS of 0.35 (95% CI 0.27-0.46; p < 0.00001) versus 0.81 for MSS patients. PFS showed a 64% reduced risk of progression (HR = 0.36, 95% CI 0.28-0.46; p < 0.0001). Subgroup analyses highlighted PFS benefits across tumor types: colorectal (HR = 0.28, 95% CI 0.11-0.73), gastric (HR = 0.43, 95% CI 0.27-0.68), and endometrial cancers (HR = 0.34, 95% CI 0.27-0.42).</p><p><strong>Conclusions: </strong>This meta-analysis establishes MSI-H as a predictive biomarker for ICIs, supporting its role in therapy selection and underscoring the need for MSI-H/dMMR-focused clinical trials.</p>","PeriodicalId":9595,"journal":{"name":"Cancer Immunology, Immunotherapy","volume":"74 4","pages":"122"},"PeriodicalIF":4.6,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11861458/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143490867","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":"Study on pathological factors affecting the sensitivity of neoadjuvant therapy in hypopharyngeal cancer.","authors":"Gaofei Yin, Nuan Li, Xiaohong Chen, Yang Zhang, Zhigang Huang, Wei Guo","doi":"10.1007/s00262-025-03957-w","DOIUrl":"10.1007/s00262-025-03957-w","url":null,"abstract":"<p><strong>Objective: </strong>Hypopharyngeal squamous cell carcinoma (HSCC) is a highly malignant tumor type in the head and neck region. In recent years, neoadjuvant therapy has significantly improved the laryngeal preservation rate among patients. However, there are variations in the efficacy of neoadjuvant therapy, and the identification of reliable predictive biomarkers for its efficacy remains a challenging research focus. This study aims to explore the correlation between the expression of P53, P16, and Ki67 and the response to neoadjuvant therapy.</p><p><strong>Methods: </strong>A retrospective analysis was conducted on 120 patients who underwent neoadjuvant therapy at Beijing Tongren Hospital, Capital Medical University, from January 2021 to June 2024. Patients were grouped based on their treatment response and the type of neoadjuvant therapy received. Group analysis were employed to assess the predictive value of P53, P16, and Ki67 for treatment efficacy across different neoadjuvant therapy groups.</p><p><strong>Results: </strong>A total of 120 patients were included in the study, with 60 patients each in the good response and poor response groups. The study comprised three neoadjuvant therapy groups: neoadjuvant chemotherapy, neoadjuvant targeted therapy combined with chemotherapy, and neoadjuvant immunotherapy combined with chemotherapy. Each group had 20 patients with good and poor responses, respectively. Among patients with P53 positivity, the effective rate after neoadjuvant therapy was 35.94%, significantly lower than the 66.07% observed in P53negative patients (p = 0.0017). For P16 positivity, the effective rate was 28.57%, lower than the 52.83% in P16negative patients (p = 0.0880). For patients with Ki67 < 60%, the effective rate was 33.33%, significantly lower than the 66.67% in those with Ki67 ≥ 60% (p = 0.0005). Comprehensively evaluate confirmed that P53 positivity and Ki67 < 60% were associated with poor response to neoadjuvant therapy, while P53 negativity and Ki67 ≥ 60% were associated with good response.</p><p><strong>Conclusion: </strong>Our findings suggest that the combination of P53 and P16 can be used as a preliminary tool to assess the efficacy of neoadjuvant therapy in patients with HSCC. Specifically, patients with P53 positivity and Ki67 < 60% tend to have lower sensitivity to neoadjuvant therapy. Further research may be needed to clarify the precise role of P16 in HSCC.</p>","PeriodicalId":9595,"journal":{"name":"Cancer Immunology, Immunotherapy","volume":"74 4","pages":"118"},"PeriodicalIF":4.6,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11861825/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143490886","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":"CDX2 and SATB2 loss are associated with myeloid cell infiltration and poor survival in colorectal cancer.","authors":"Päivi Sirniö, Hanna Elomaa, Anne Tuomisto, Ville K Äijälä, Henna Karjalainen, Meeri Kastinen, Vilja V Tapiainen, Onni Sirkiä, Maarit Ahtiainen, Olli Helminen, Erkki-Ville Wirta, Jukka Rintala, Sanna Meriläinen, Juha Saarnio, Tero Rautio, Toni T Seppälä, Jan Böhm, Jukka-Pekka Mecklin, Markus J Mäkinen, Juha P Väyrynen","doi":"10.1007/s00262-025-03964-x","DOIUrl":"10.1007/s00262-025-03964-x","url":null,"abstract":"<p><strong>Background: </strong>Caudal-type homeobox 2 (CDX2) and special AT-rich sequence-binding protein 2 (SATB2) are transcription factors playing important roles in intestinal homeostasis and participating in the regulation of intestinal inflammation. In colorectal cancer (CRC), reduced expression levels of CDX2 and SATB2 have been associated with poor differentiation and worse survival. However, their prognostic significance still needs further clarification, and the associations between CDX2 and SATB2 and immune cell infiltration into the CRC microenvironment are largely unknown.</p><p><strong>Methods: </strong>We analyzed CDX2 and SATB2 expression in two large cohorts of stages I-IV CRC patients (N = 2302) and analyzed their associations with clinicopathologic parameters, the density of local immune cells (determined with three multiplex immunohistochemistry panels and conventional immunohistochemistry), and survival.</p><p><strong>Results: </strong>In mismatch repair-proficient tumors, reduced CDX2 and SATB2 expression were associated with higher densities of immature monocytic cells, macrophages, and M2-like macrophages. Low expression of CDX2 was associated with shorter cancer-specific survival independent of conventional prognostic parameters in both cohorts. In the larger cohort, adjusted hazard ratio (HR) for negative (vs. high) CDX2 expression was 3.62 (95% CI 2.08-6.31, p_trend < 0.0001), and adjusted HR for negative (vs. high) SATB2 level was 1.61 (95% CI 0.97-2.67, p_trend= 0.002).</p><p><strong>Conclusion: </strong>This study indicates that reduced CDX2 and SATB2 expression levels are associated with myeloid cell infiltration in the CRC microenvironment and represent markers for poor outcome. These findings highlight the potential of CDX2 and SATB2 as biomarkers for classifying CRC patients and support their role in regulating the tumor microenvironment.</p>","PeriodicalId":9595,"journal":{"name":"Cancer Immunology, Immunotherapy","volume":"74 4","pages":"111"},"PeriodicalIF":4.6,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11861821/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143490772","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":"Comparison of neoadjuvant chemoimmunotherapy with planned surgery and concurrent chemoradiation followed by immunotherapy for potentially resectable stage III non-small-cell lung cancer: a retrospective study.","authors":"Yana Qi, Xiaoyang Zhai, Qinhao Xu, Yuqin Jin, Yingfan Guo, Miaoqing Zhao, Hui Zhu, Hongbo Guo","doi":"10.1007/s00262-025-03961-0","DOIUrl":"10.1007/s00262-025-03961-0","url":null,"abstract":"<p><strong>Objective: </strong>Despite the promising potential of neoadjuvant chemoimmunotherapy for non-small cell lung cancer (NSCLC), there is limited consensus on the optimal treatment strategy for potentially resectable NSCLC. This study aimed to evaluate the efficacy and safety of neoadjuvant chemoimmunotherapy (neoCT/IO) with planned surgery versus definitive concurrent chemoradiation followed by immunotherapy (cCRT + IO) in potentially resectable stage III NSCLC.</p><p><strong>Methods: </strong>This retrospective study analyzed data from patients with potentially resectable stage III NSCLC who underwent neoCT/IO with planned surgery or cCRT + IO between March 2020 and June 2023. Propensity score matching (PSM) was used to balance heterogeneity between groups. Efficacy outcomes, safety profiles and patterns of disease recurrence were assessed.</p><p><strong>Results: </strong>A total of 308 eligible patients were included in this study, of whom 195 (63.3%) underwent neoCT/IO and 113 (36.7%) received cCRT + IO. The neoCT/IO group consisted of patients who underwent neoCT/IO + Surgery and neoCT/IO + Radiotherapy. After 1:1 PSM, each group consisted of 105 patients. The median progression-free survival (PFS) was 25.9 months in the cCRT + IO group and not reached (NR) in the neoCT/IO group (hazard ratio: 2.91, 95% confidence interval: 1.77-4.78; p < 0.001). Median overall survival (OS) was NR in either group, with 3-year OS rates of 87.5% in the neoCT/IO group and 75.0% in the cCRT + IO group (p = 0.22). The incidence of grade 3/4 treatment-related adverse events was similar in both groups, except for a higher incidence of grade 3/4 hematological toxicity in the cCRT + IO group.</p><p><strong>Conclusions: </strong>For patients with potentially resectable stage III NSCLC, neoCT/IO appears to be a safe approach and may offer better survival outcomes compared with cCRT + IO. Prospective randomized trials are needed to further validate these findings.</p>","PeriodicalId":9595,"journal":{"name":"Cancer Immunology, Immunotherapy","volume":"74 4","pages":"119"},"PeriodicalIF":4.6,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11861850/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143490773","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":"Continuous immunotherapy beyond disease progression in patients with advanced non-small cell and small cell lung cancer.","authors":"Jing Cheng, Wenwen Kang, Yueying Chen, Luyun Pan, Hedong Han, Tangfeng Lv","doi":"10.1007/s00262-025-03958-9","DOIUrl":"10.1007/s00262-025-03958-9","url":null,"abstract":"<p><strong>Background: </strong>The benefits of continuing immunotherapy beyond disease progression in advanced non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) remain uncertain, along with the specific patient subgroups that may gain the most from this approach. This retrospective study aims to evaluate the efficacy of this approach and identify target patient populations likely to benefit.</p><p><strong>Methods: </strong>We collected data from patients with NSCLC and SCLC who experienced disease progression following initial immune checkpoint inhibitor (ICI) treatment from January 2020 to December 2023. Patients were categorized based on second-line treatment: those receiving immunotherapy beyond progression (IBP) and those receiving non-immunotherapy beyond progression (NIBP). Survival outcomes and treatment safety were compared between these two groups.</p><p><strong>Results: </strong>A total of 150 patients were included, with 111 NSCLC patients (IBP: n = 78, NIBP: n = 33) and 39 SCLC patients (IBP: n = 31, NIBP: n = 8). Significant differences in median progression-free survival (PFS) and overall survival (OS) were found in patients with driver gene-negative NSCLC (mPFS: 4.7 vs 1.3 months, HR = 0.29, P < 0.01; mOS: 11.03 vs 2.63 months, HR = 0.13, P < 0.001) and SCLC (mPFS: 3.9 vs 2.1 months, HR = 0.38, P = 0.02; mOS: 9.28 vs 2.27 months, HR = 0.23, P < 0.01). Additionally, among driver gene-negative NSCLC patients, achieving a partial response (PR) or stable disease (SD) during initial immunotherapy was associated with improved effectiveness of continued immunotherapy beyond progression.</p><p><strong>Conclusions: </strong>Continued immunotherapy as a second-line treatment may benefit patients with driver gene-negative NSCLC and SCLC who have progressed after initial immunotherapy.</p>","PeriodicalId":9595,"journal":{"name":"Cancer Immunology, Immunotherapy","volume":"74 4","pages":"124"},"PeriodicalIF":4.6,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11861770/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143490775","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":"Comprehensive analysis and experimental validation of disulfidptosis-associated prognostic signature and immune microenvironment characterization of gastric cancer.","authors":"Huangjie Zhang, Jinguo Hu, Yuanqiang Li, Yanyang Liu, Huize Shen, Zeng Wang, Qinglin Li","doi":"10.1007/s00262-024-03883-3","DOIUrl":"10.1007/s00262-024-03883-3","url":null,"abstract":"<p><strong>Background: </strong>Gastric cancer (GC) is one of the most common causes of cancer-related death worldwide. As a novel form of programmed cell death, disulfidptosis is characterized by excessive cysteine accumulation, disulfide stress and actin destruction. There is evidence that targeting disulfidptosis is a promising anticancer strategy. Further improvement of GC risk stratification based on disulfidptosis has positive clinical significance.</p><p><strong>Methods: </strong>We analyzed the expression levels of disulfidptosis-associated genes (DPAGs) in normal and GC tissues and characterized the molecular subtypes of GC patients. Based on the characteristics of DPAG subtypes, differentially expressed prognosis-related genes were selected by LASSO-univariate Cox analysis and multivariate Cox analysis analyzed to establish a prognostic model. Using single-cell sequencing analysis reveals the cell subpopulation for GC. The function of the selected target in GC was verified by in vitro experimental means, including siRNA, qRT-PCR, Western blot, CCK-8, and Transwell assay.</p><p><strong>Results: </strong>DPAG score was verified to be an independent prognostic factor of GC and was significantly associated with poor prognosis of gastric cancer. Subsequent studies on subgroup immunoinfiltration characteristics, drug sensitivity analysis, immunotherapy response and somatic mutation characteristics of DPAG score comprehensively confirmed the potential guiding significance of DPAG score for individualized treatment of gastric cancer patients. Single-cell sequencing analysis revealed the expression characteristics of DPAG-related prognostic signatures across cell subpopulations. In vitro experiments showed APC11, as one of the selected DPAGs, was highly expressed in gastric cancer, and knockdown of APC11 could significantly inhibit the proliferation and migration of GC cells, demonstrating the reliability of bioinformatics results.</p><p><strong>Conclusion: </strong>The results of this study provide a new perspective for exploring the role of disulfidptosis in the occurrence and development of GC.</p>","PeriodicalId":9595,"journal":{"name":"Cancer Immunology, Immunotherapy","volume":"74 4","pages":"116"},"PeriodicalIF":4.6,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11861452/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143490774","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":"Monitoring peripheral blood data supports the prediction of immunotherapy response in advanced non-small cell lung cancer based on real-world data.","authors":"Ana D Ramos-Guerra, Benito Farina, Jaime Rubio Pérez, Anna Vilalta-Lacarra, Jon Zugazagoitia, Germán Peces-Barba, Luis M Seijo, Luis Paz-Ares, Ignacio Gil-Bazo, Manuel Dómine Gómez, María J Ledesma-Carbayo","doi":"10.1007/s00262-025-03966-9","DOIUrl":"10.1007/s00262-025-03966-9","url":null,"abstract":"<p><p>The identification of non-small cell lung cancer (NSCLC) patients who will benefit from immunotherapy remains a clinical challenge. Monitoring real-world data (RWD) in the first cycles of therapy may provide a more accurate representation of response patterns in a real-world setting. We propose a multivariate Bayesian joint model using generalized linear mixed effects, trained and validated on RWD from 424 advanced NSCLC patients retrospectively collected from three clinical centers. Center1 was used as training ( <math><mrow><mi>N</mi> <mo>=</mo> <mn>212</mn></mrow> </math> ), while Center2 and Center3 were used as independent testing sets ( <math><mrow><mi>N</mi> <mo>=</mo> <mn>137</mn></mrow> </math> and <math><mrow><mi>N</mi> <mo>=</mo> <mn>75</mn></mrow> </math> , respectively). Peripheral blood data (PBD) were collected at baseline and at three follow-up time points, alongside demographic and epidemiologic features. Six models were trained to predict progression-free survival at 6 months, PFS(6), using different number of longitudinal samples (baseline, two, or four time points) of the neutrophil-to-lymphocyte ratio (NLR) or a multivariate feature selection. Long-term predictions at 12 and 24 months were also evaluated. Prediction accuracy was measured using the area under the receiver operating characteristic curve (AUC). The proposed model significantly improved prediction performance, achieving AUCs of 0.870, 0.804 and 0.827 at 6, 12 and 24 months for Center2, and 0.824, 0.822 and 0.667 for Center3. There was also a significant difference in PFS and overall survival (OS) between predicted response groups, defined by a 6-month PFS cutoff (log-rank test <math><mrow><mi>p</mi> <mo><</mo> <mn>0.001</mn></mrow> </math> ). Our study suggests that the integration of multiple biomarkers and monitored PBD in an RWD-based Bayesian joint model framework significantly improves immunotherapy response prediction in advanced NSCLC compared to conventional approaches involving biomarker data at baseline only.</p>","PeriodicalId":9595,"journal":{"name":"Cancer Immunology, Immunotherapy","volume":"74 4","pages":"120"},"PeriodicalIF":4.6,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11861465/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143490869","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":"Exploring correlations between gut mycobiome and lymphocytes in melanoma patients undergoing anti-PD-1 therapy.","authors":"Natalia Szóstak, Michał Budnik, Katarzyna Tomela, Luiza Handschuh, Anna Samelak-Czajka, Bernadeta Pietrzak, Marcin Schmidt, Mariusz Kaczmarek, Łukasz Galus, Jacek Mackiewicz, Andrzej Mackiewicz, Piotr Kozlowski, Anna Philips","doi":"10.1007/s00262-024-03918-9","DOIUrl":"10.1007/s00262-024-03918-9","url":null,"abstract":"<p><p>Research has shown that the microbiome can influence how the immune system responds to melanoma cells, affecting the course of the disease and the outcome of the therapy. Here, we used the metagenomic approach and flow cytometry analyses of blood cells to discover correlations between gut fungi of metastatic melanoma patients enrolled in anti-PD-1 therapy and lymphocytes in their blood.We analyzed the patterns of associations before the first administration of anti-PD-1 therapy (BT, n = 61) and in the third month of the therapy (T3, n = 37), allowing us to track changes during treatment. To understand the possible impact of gut fungi on the efficacy of anti-PD-1 therapy, we analyzed the associations in clinical beneficiaries (CB, n = 37) and non-beneficiaries (NB, n = 24), as well as responders (R, n = 28) and non-responders (NR, n = 33).Patients with LDH < 338 units/L, overall survival (OS) > 12, CB, as well as R, had lower levels of Shannon diversity (p = 0.02, p = 0.05, p = 0.05, and p = 0.03, respectively). We found that the correlation pattern between intestinal fungi and lymphocytes was specific to the type of response, positive or negative. When comparing CB and NB groups, correlations with opposite directions were detected for C. albicans, suggesting a response-specific immune reaction. For CB, M. restricta exhibited a set of correlations with different types of lymphocytes, with prevalent positive correlations, suggesting a robust immune response in the CB group. This result extends our former research, where M. restricta and C. albicans were associated with an increased risk of melanoma progression and a poorer response to anti-PD-1 treatment.</p>","PeriodicalId":9595,"journal":{"name":"Cancer Immunology, Immunotherapy","volume":"74 4","pages":"110"},"PeriodicalIF":4.6,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11861499/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143490777","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":"From silent partners to potential therapeutic targets: macrophages in colorectal cancer.","authors":"Hayat Khizar, Kamran Ali, Jianwei Wang","doi":"10.1007/s00262-025-03965-w","DOIUrl":"10.1007/s00262-025-03965-w","url":null,"abstract":"<p><p>Cancer cells grow and survive in the tumor microenvironment, which is a complicated process. As a key part of how colorectal cancer (CRC) progresses, tumor-associated macrophages (TAMs) exhibit a double role. Through angiogenesis, this TAM can promote the growth of cancers. Although being able to modify and adjust immune cells is a great advantage, these cells can also exhibit anti-cancer properties including direct killing of cancer cells, presenting antigens, and aiding T cell-mediated responses. The delicate regulatory mechanisms between the immune system and tumors are composed of a complex network of pathways regulated by several factors including hypoxia, metabolic reprogramming, cytokine/chemokine signaling, and cell interactions. Decoding and figuring out these complex systems become significant in building targeted treatment programs. Targeting TAMs in CRC involves disrupting chemokine signaling or adhesion molecules, reprogramming them to an anti-tumor phenotype using TLR agonists, CD40 agonists, or metabolic modulation, and selectively removing TAM subsets that promote tumor growth. Multi-drug resistance, the absence of an accurate biomarker, and drug non-specificity are also major problems. Combining macrophage-targeted therapies with chemotherapy and immunotherapy may revolutionize treatment. Macrophage studies will advance with new technology and multi-omics methodologies to help us understand CRC and build specific and efficient treatments.</p>","PeriodicalId":9595,"journal":{"name":"Cancer Immunology, Immunotherapy","volume":"74 4","pages":"121"},"PeriodicalIF":4.6,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11861851/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143490778","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}