Immunology最新文献

{"title":"Chronological Effects of Immune Checkpoint Inhibitors in Non-Small Cell Lung Cancer","authors":"Xinyue Guo,&nbsp;Lanqun Qin,&nbsp;Xinmeng Wang,&nbsp;Qian Geng,&nbsp;Dongqing Li,&nbsp;Yingying Lu,&nbsp;Hua Jiang","doi":"10.1111/imm.13897","DOIUrl":"10.1111/imm.13897","url":null,"abstract":"<div>\u0000 \u0000 <p>Circadian rhythm is a physiological process that oscillates in a 24 h cycle. It has a complex connection with the function of the human immune system and even with the development of tumours. Previous studies demonstrated the time-dependent effects of chemotherapy and radiotherapy; however, there are few studies on the timing effects of immunotherapy. Here, we explored the differences in the efficacy of immune checkpoint inhibitors (ICIs) administered at different circadian rhythm times in non-small cell lung cancer (NSCLC). C57BL/6N lung Lewis cancer mice models were constructed. Then, mice were intraperitoneally injected with saline or anti-PD-1 antibody at 7 AM or 7 PM, The expression of PD-L1 was detected by flow cytometry, and the expressions of clock gene BMAL1 and PER2 were detected by polymerase chain reaction (PCR) after treatment. A retrospective analysis was conducted on patients with NSCLC who received ICIs in our department from June 2020 to December 2022. Animal experiments showed that mice treated with ICIs in the morning showed slower tumour growth and smaller tumour volumes than those in the afternoon, accompanied by increased expression of BMAL1 and PER2 and suppression of PD-L1 expression. Retrospective analysis showed that patients who received ICIs in the afternoon (after 12:00) had significantly longer progression-free survival than those in the morning (before 12:00) (median was 16.5 months versus 9.8 months, respectively, <i>p =</i> 0.031, hazard ratio = 1.87). These findings suggest that immunotherapy may have time dependence, offering a novel therapeutic strategy.</p>\u0000 </div>","PeriodicalId":13508,"journal":{"name":"Immunology","volume":"174 4","pages":"402-410"},"PeriodicalIF":4.9,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142948215","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Zinc Deficiency Reduces Intestinal Secretory Immunoglobulin A and Induces Inflammatory Responses via the Gut-Liver Axis","authors":"Takamasa Kido,&nbsp;Hiroyuki Yanagisawa,&nbsp;Machi Suka","doi":"10.1111/imm.13896","DOIUrl":"10.1111/imm.13896","url":null,"abstract":"<div>\u0000 \u0000 <p>Nutritional zinc (Zn) deficiency could impair immune function and affect bowel conditions. However, the mechanism by which Zn deficiency affects the immune function of gut-associated lymphoid tissue (GALT) remains unclear. We investigated how Zn deficiency affects the function of GALT and level of secretory IgA (sIgA), a key component of the intestinal immune barrier, its underlying mechanisms, and whether Zn deficiency induces bacterial translocation to the liver. As previous research has indicated that interleukin (IL)-4 administration or Zn supplementation has a beneficial effect on the spleen of Zn-deficient rats, we investigated whether these supplements reverse the GALT immune system. Five-week-old male rats were fed a standard diet, Zn-deficient diet supplemented with saline or IL-4 for 6 weeks, or Zn-deficient diet followed by a standard diet for 4 weeks. Zn deficiency suppressed sIgA secretion in the intestinal tract by affecting GALT function and induced inflammatory responses through bacterial translocation to the liver via the portal vein. Furthermore, IL-4 administration and Zn supplementation in rats with Zn deficiency elicited comparable beneficial effects on GALT function, suggesting that the administration of either IL-4 or Zn could prevent inflammatory response via bacterial translocation to the liver.</p>\u0000 </div>","PeriodicalId":13508,"journal":{"name":"Immunology","volume":"174 3","pages":"363-373"},"PeriodicalIF":4.9,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142948219","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effective Mucosal Adjuvantation of the Intranasal Enterovirus A71 Vaccine With Zymosan","authors":"Chiao-Li Chin,&nbsp;Yu-Li Lin,&nbsp;Pei-Yun Cheng,&nbsp;Ping Lee,&nbsp;Bor-Luen Chiang","doi":"10.1111/imm.13895","DOIUrl":"10.1111/imm.13895","url":null,"abstract":"<div>\u0000 \u0000 <p>Enterovirus A71 (EV-A71) has caused hand, foot, and mouth disease with an increased prevalence of neurological complications and acute mortality, threatening young children around the globe. By provoking mucosal immunity, intranasal vaccination has been suggested to prevent EV-A71 infection. However, antigens delivered via the nasal route usually fail to induce a protective memory response. Zymosan has been identified to activate multiple pattern recognition receptors to orchestrate innate and adaptive immunity. Herein, we aimed to investigate the capacity of zymosan to strengthen the vaccine response induced by an intranasal EV-A71 vaccine. First, we confirmed its remarkable capacity to ignite innate signaling by upregulating cytokine production in primary DCs in vitro. Second, we verified its capacity to promote the vaccine immunogenicity in vivo after triple vaccination with EV-A71, especially with the notable induction of virus-specific IgA at multiple mucosae and the IL-17-producing splenic population after antigen reencounter. Lastly, we validated its capacity to improve vaccine efficacy in vivo after dual vaccination by furnishing neonatal protection against lethal infection. Our findings show that zymosan, at a preferable dosage, could augment the benefits of the intranasal vaccination to tackle EV-A71 infection. This research provides a feasible strategy for preventing EV-A71 infection with severe complications and contributes to the development of nasal spray vaccination.</p>\u0000 </div>","PeriodicalId":13508,"journal":{"name":"Immunology","volume":"174 3","pages":"349-362"},"PeriodicalIF":4.9,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142948216","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prophylactic Peanut Allergen Ara h 6 Sublingual Immunotherapy Drives Expansion of FoxP3\u0000 +Helios− Regulatory T Cells in the Absence of Allergen-Specific IgA","authors":"Jeppe Madura Larsen,&nbsp;Emma Alberte Lundsgaard,&nbsp;Niels Banhos Danneskiold-Samsøe,&nbsp;Si Brask Sonne,&nbsp;Neil Marcus Rigby,&nbsp;Alan Robert Mackie,&nbsp;Karsten Kristiansen,&nbsp;Katrine Lindholm Bøgh","doi":"10.1111/imm.13883","DOIUrl":"10.1111/imm.13883","url":null,"abstract":"<p>Insights into the underlying immunological mechanisms of prophylactic sublingual immunotherapy (SLIT) may support the development of new strategies for improved prevention and treatment of food allergy. Here, we investigated the humoral, regulatory and sublingual tissue immune response to prophylactic SLIT administration of a single purified peanut allergen in Brown Norway (BN) rats. BN rats received daily sublingual administration of peanut allergen Ara h 6 for three weeks. Suppression of sensitisation was evaluated by subsequent intraperitoneal administration of Ara h 6. Ara h 6-specific IgE, IgA, IgG1 and IgG2a-c levels were measured in serum. The frequency of regulatory T (Treg) cells was analysed using flow cytometry. The sublingual tissue response to Ara h 6 was analysed by transcriptional profiling using mRNA-sequencing. Ara h 6 SLIT protected rats from subsequent sensitisation without inducing a detectable humoral immune response (Ara h 6-specific IgE, IgA, IgG1 and IgG2a-c) in serum. SLIT furthermore promoted the relative expansion of induced Helios⁻ Treg cells within the conventional CD4⁺CD25⁺FoxP3⁺ Treg population in sublingual draining lymph nodes and blood. In conclusion, prophylactic Ara h 6 SLIT drives the relative expansion of induced Helios⁻ Treg cells in the absence of Ara h 6-specific IgA highlighting a potential novel IgA-independent Treg-related immune response at the sublingual mucosal site.</p>","PeriodicalId":13508,"journal":{"name":"Immunology","volume":"174 3","pages":"340-348"},"PeriodicalIF":4.9,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/imm.13883","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142948217","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integration of Immune Responses and Transcriptomic Signatures Reveals the Efficacy of Maternal Genetic Vaccination in a Pregnant Model and Its Neonates","authors":"Sohail Ahmed,&nbsp;Guiqiong Liu,&nbsp;Amber Sadiq,&nbsp;Umar Farooq,&nbsp;Huiguo Yang,&nbsp;Liu Yongbin,&nbsp;Sha Yiyu,&nbsp;Wang Xiaodong,&nbsp;Xunping Jiang","doi":"10.1111/imm.13880","DOIUrl":"https://doi.org/10.1111/imm.13880","url":null,"abstract":"<div>\u0000 \u0000 <p>Maternal vaccination is essential for safeguarding both mother and foetus from infectious diseases. This study investigated the immunogenicity and efficacy of a maternal ORF-<i>B2L</i> genetic vaccine in a pregnant rat model, focusing on maternal–neonatal immune modulation, placental and neonatal spleen transcriptomics and the underlying mechanisms contributing to neonatal immune development. Female rats received intramuscular injections of either a gene vaccine (GV) containing 200 μg of recombinant ORF-<i>B2L</i> DNA and 50 μg of a subunit protein or an empty plasmid as a control. Results showed significantly higher levels of specific anti-<i>B2L</i> antibodies and Th1 and Th2 cytokine levels in both maternal and neonatal sera from the GV group compared to the control group (<i>p</i> &lt; 0.05). Transcriptome analysis identified 1295 differentially expressed genes (DEGs) in the placenta and 998 DEGs in the neonatal spleen, with upregulated pathways associated with immune cell recruitment, cytokine signalling and hormone regulation in the GV group. Notably, upregulated DEGs such as <i>TLR4</i>, <i>ESR1</i> and various cytokine/chemokine-related genes in the placenta suggest enhanced immune regulation and foetal protection. In the neonatal spleen, increased expression of <i>IL-1β</i>, <i>IL-6</i>, <i>IL-10</i> and <i>CD69</i> indicates enhanced T and B cell development and pathogen defence. The upregulation of <i>IL-1β</i> suggests a Th1 response, while elevated <i>IL-10</i> indicates a potential Th2-biased immunity, reflecting a balanced Th1/Th2 response that is crucial for effective adaptive immunity. Overall, maternal ORF-<i>B2L</i> genetic vaccination induces a robust immune response, enhancing maternal-foetal protection and shaping neonatal immune responses, offering valuable insights for optimizing maternal vaccination strategies.</p>\u0000 </div>","PeriodicalId":13508,"journal":{"name":"Immunology","volume":"174 3","pages":"322-339"},"PeriodicalIF":4.9,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143186484","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Newly Found Rat CD103\u0000 − Dendritic Cells Represent a Highly Immunogenic Subpopulation of Type-2 Conventional Dendritic Cells, Corresponding to Known Dendritic Cell Subsets in Mice and Humans","authors":"Yasushi Sawanobori,&nbsp;Tadayuki Ogawa,&nbsp;Hisashi Ueta,&nbsp;Yusuke Kitazawa,&nbsp;Nobuko Tokuda","doi":"10.1111/imm.13893","DOIUrl":"10.1111/imm.13893","url":null,"abstract":"<div>\u0000 \u0000 <p>Dendritic cells (DCs), the primary antigen-presenting cells, have traditionally been identified by CD103 molecules in rats, whereas mouse and human DCs are identified by CD11c molecules. However, this history does not preclude the existence of CD103⁻ DCs in rats. To explore this possibility, we examined MHCII⁺ cells in rat spleen and thymus, identifying a novel population of CD103⁻MHCII⁺CD45R⁻CD172a⁺ cells. These cells are negative for CD103 and B cell marker CD45R, but positive for the type-2 conventional DC (cDC2) marker CD172a. Transcriptomic analyses revealed that they represent a subpopulation of cDC2. Additionally, gene set enrichment analysis predicted enhanced immunogenic activities for this novel population compared to known rat cDC2s. Mixed leukocyte reaction assays confirmed that the rat CD103⁻ cDC2s induce T cell proliferation more effectively than other DC subsets, suggesting enhanced immunogenic potential. In reaggregated thymic organ culture assays, both the rat CD103⁻ and CD103⁺ cDC2 subsets suppressed the total number of generated thymocytes and skewed the differentiation toward CD8 single-positive cells. Comparisons with previously published single-cell RNA-sequencing datasets showed that the rat CD103⁻ cDC2 subset shares markers and GO terms of known mouse and human cDC2 subpopulations: cDC2a, cDC2b, inf-cDC2, and moDC. In contrast, the classic rat CD103⁺ cDC2 subset expresses only cDC2a markers. These findings provide new insights into DC subpopulations, particularly in species other than mice and humans, where much remains to be uncovered.</p>\u0000 </div>","PeriodicalId":13508,"journal":{"name":"Immunology","volume":"174 4","pages":"384-401"},"PeriodicalIF":4.9,"publicationDate":"2025-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142926999","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Co-Expression of Dominant-Negative TGF-β Receptor 2 Enhances the Therapeutic Efficacy of Novel TREM1/DAP12-BB-Based CAR-T Cells in Solid Tumours","authors":"Sichao Zhu,&nbsp;Jianping Hu,&nbsp;Jie Lin,&nbsp;Chen Wang,&nbsp;Enxiu Wang","doi":"10.1111/imm.13888","DOIUrl":"10.1111/imm.13888","url":null,"abstract":"<div>\u0000 \u0000 <p>Chimeric antigen receptor (CAR) T-cell therapy has exhibited remarkable efficacy in the treatment of haematological malignancies, yet its application in solid tumours is hindered by the immunosuppressive tumour microenvironment (TME). In this study, a novel SS1-TREM1/DAP12-BB CAR-T cell was devised to target ovarian cancer and further engineered to co-express the dominant-negative TGF-β receptor 2 (DNR) to combat CAR-T cell exhaustion in TME. The incorporation of DNR effectively blocked TGF-β signalling, thereby enhancing CAR-T cell survival and antitumor activity in a TGF-β1-rich environment. In vivo evaluations demonstrated that DNR co-expression potentiated the antitumor efficacy of TREM1/DAP12-BB CAR-T cells and conferred resilience against tumour rechallenge. These findings underscore the broad potential of DNR co-expression in CAR design, presenting a novel therapeutic strategy for patients with recurrent ovarian cancer.</p>\u0000 </div>","PeriodicalId":13508,"journal":{"name":"Immunology","volume":"174 3","pages":"310-321"},"PeriodicalIF":4.9,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142921578","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Interactions of NK Cells and Macrophages: From Infections to Cancer Therapeutics","authors":"Vishakha Hooda,&nbsp;Alpana Sharma","doi":"10.1111/imm.13886","DOIUrl":"10.1111/imm.13886","url":null,"abstract":"<p>The interaction between immune cells brings a consequence either on their role and functioning or the functioning of the other immune cells, modulating the whole mechanistic pathway. The interaction between natural killer (NK) cells and macrophages is one such interaction which is relatively less explored amongst diseased conditions. Their significance comes from their innate nature and secretion of large proportions of cytokines and chemokines which results in influencing adaptive immune responses. Their interplay can lead to several functional outcomes such as NK cell activation/inhibition, increased cytotoxicity and IFNγ release by NK cells, inhibition of macrophage function, etc. This paper delves into the interaction amongst NK cells and macrophages via different receptor-ligands and cytokines, particularly emphasising microbial infections and tumours. The review has the potential to uncover new insights and approaches that could lead to the development of innovative therapeutic tools and targets.</p>","PeriodicalId":13508,"journal":{"name":"Immunology","volume":"174 3","pages":"287-295"},"PeriodicalIF":4.9,"publicationDate":"2024-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/imm.13886","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142909536","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"FOXP3 Transcriptionally Activates Fatty Acid Scavenger Receptor CD36 in Tumour-Induced Treg Cells","authors":"Subhanki Dhar,&nbsp;Tania Sarkar,&nbsp;Sayantan Bose,&nbsp;Subhadip Pati,&nbsp;Dwaipayan Chakraborty,&nbsp;Dia Roy,&nbsp;Abir K. Panda,&nbsp;Aharna Guin,&nbsp;Sumon Mukherjee,&nbsp;Kuladip Jana,&nbsp;Diptendra K. Sarkar,&nbsp;Gaurisankar Sa","doi":"10.1111/imm.13887","DOIUrl":"10.1111/imm.13887","url":null,"abstract":"<div>\u0000 \u0000 <p>The host immune system is adapted in a variety of ways by tumour microenvironment and growing tumour interacts to promote immune escape. One of these adaptations is manipulating the metabolic processes of cells in the tumour microenvironment. The growing tumour aggressively utilise glucose, its primary energy source available in tumour site, and produce lactate by Warburg effect. In such a hostile environment, tumour-infiltrating immune cells are unable to survive metabolically. Tumour-infiltrating CD4⁺ Treg cells, on the other hand, adapted to an alternative energy-generating system, switching from the highly-competitive glucose to the fatty-acid metabolic pathway, by down-regulating glucose-metabolising genes and up-regulating fatty-acid metabolising genes. Tregs with high-levels of the fatty acid scavenger receptor CD36, a key component of the fatty-acid metabolic pathway, aided this metabolic shift. Treg cell formation was hampered when the fatty-acid metabolic pathway was disrupted, showing that it is necessary for Treg cell development. FOXP3, the Treg lineage-specific transcription factor, regulates fatty-acid metabolism by inducing <i>CD36</i> transcription. A high-fat diet enhanced Treg development while suppressing anti-tumour immunity, whereas a low-fat diet suppressed Treg development. The altered metabolism of tumour-infiltrating Treg cells enables their rapid generation and survival in the hostile tumour microenvironment, aiding cancer progression. Fascinatingly, mice fed with a low-fat diet showed a positive prognosis with chemotherapy than mice fed with a high-fat diet. Thus, a maximum efficacy of chemotherapy might be achieved by altering diet composition during chemotherapy, providing a promising indication for future cancer treatment.</p>\u0000 </div>","PeriodicalId":13508,"journal":{"name":"Immunology","volume":"174 3","pages":"296-309"},"PeriodicalIF":4.9,"publicationDate":"2024-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142907023","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ITGB4/BNIP3 Activates Autophagy and Reduces MHC-I Expression to Mediate Tumour Immune Escape in Pancreatic Cancer Cell Lines","authors":"Xianfei Zhou,&nbsp;Fan Yang,&nbsp;Luoshun Huang,&nbsp;Yisheng Ling,&nbsp;Renwei Xing,&nbsp;Jie Lu,&nbsp;Hanqiu Nie","doi":"10.1111/imm.13890","DOIUrl":"10.1111/imm.13890","url":null,"abstract":"<div>\u0000 \u0000 <p>This study attempted to identify the relevant pathways involved in autophagy activation of pancreatic cancer and explore the mechanisms underlying immune evasion. Western blot (WB) was used to detect the expression of ITGB4, BNIP3, autophagy-related proteins and MHC-I. Co-immunoprecipitation (Co-IP) was used to verify the binding mode of ITGB4 and BNIP3. Flow cytometry was used to detect the expression of MHC-I on the cell membrane. Transmission electron microscope (TEM) was used to observe cell autophagy. Confocal microscopy was used to observe the co-localisation relationship between MHC-I and autophagosomes in cells. ELISA was used to detect the level of lactate dehydrogenase and granzyme B in a tumour cell-CD8⁺ T-cell co-culture system. Mouse syngeneic transplant tumour model and orthotopic tumour model were constructed and treated with PD-1 monoclonal antibody to observe tumour growth. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to detect the mRNA expression of ITGB4 and BNIP3 in tumour tissues. WB was used to determine the expression of autophagy-related proteins. Flow cytometry was used to detect the expression of MHC-I on cell membranes and the proportion of CD3⁺ and CD8⁺ cells. The results of Co-IP experiments showed that ITGB4 could bind to BNIP3. It was observed under confocal microscopy that activating ITGB4/BNIP3 could promote the phagocytosis of MHC-I by autophagosomes. Finally, the subcutaneous tumour transplantation and orthotopic tumour experiments in mice demonstrated the downregulation of ITGB4 significantly improved the therapeutic effect of PD-1 antibodies on pancreatic cancer. In pancreatic cancer cells, autophagy is positively correlated with the ITGB4-BNIP3 complex protein expression level. Autophagy diminishes the protein expression of MHC-I, thereby promoting immune escape in pancreatic cancer cells.</p>\u0000 </div>","PeriodicalId":13508,"journal":{"name":"Immunology","volume":"174 2","pages":"264-277"},"PeriodicalIF":4.9,"publicationDate":"2024-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142876915","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}