Frontiers in ImmunologyPub Date : 2025-10-07eCollection Date: 2025-01-01DOI: 10.3389/fimmu.2025.1685592
Chenfei Zhou, Yan Sun, Tao Liu, David P J van Dijk, Wenqi Xi, Jinling Jiang, Liting Guo, Feng Qi, Xuekun Zhang, Mengfan Jia, Jun Ji, Zhenggang Zhu, Sander S Rensen, Steven W M Olde Damink, Jun Zhang
{"title":"Clinical and body composition parameters as predictors of response to chemotherapy plus PD-1 inhibitor in gastric cancer.","authors":"Chenfei Zhou, Yan Sun, Tao Liu, David P J van Dijk, Wenqi Xi, Jinling Jiang, Liting Guo, Feng Qi, Xuekun Zhang, Mengfan Jia, Jun Ji, Zhenggang Zhu, Sander S Rensen, Steven W M Olde Damink, Jun Zhang","doi":"10.3389/fimmu.2025.1685592","DOIUrl":"https://doi.org/10.3389/fimmu.2025.1685592","url":null,"abstract":"<p><strong>Background: </strong>Predicting the treatment efficacy of programmed cell death protein 1 (PD-1) inhibitors is crucial for guiding optimal treatment plans and preventing unnecessary complications for cancer patients. We aimed to develop a prediction model using clinical and body composition parameters to identify gastric cancer (GC) patients who would respond to chemotherapy plus PD-1 antibody.</p><p><strong>Methods: </strong>Clinical data of GC patients treated with chemotherapy plus PD-1 antibody (immunotherapy cohort, n = 120) or chemotherapy alone (chemotherapy cohort, n = 82) following surgical resection were reviewed as the training set. Patients treated with chemotherapy plus PD-1 antibody at an external center were included as the validation set (n = 43). Tumor regression grade (TRG) was recorded and classified as TRG0/1 or TRG2/3 during analysis. Body composition parameters were assessed on computed tomography images at the third lumbar vertebral level using the SliceOmatic software. Univariate and multivariate analyses were performed to identify parameters associated with TRG0/1, and then a logistic regression model was developed to stratify patients into the good and poor response groups.</p><p><strong>Results: </strong>In the training set, clinical and body composition parameters between the immunotherapy cohort and chemotherapy cohort were similar. Skeletal muscle radiation attenuation (SMRA), neutrophil-to-lymphocyte ratio (NLR), and weight loss were associated with TRG0/1 in the immunotherapy cohort. Subcutaneous adipose tissue index (SATI) and metastasis were identified in the chemotherapy cohort. A logistic regression model was developed to stratify immunotherapy cohort patients into two response groups with an area under the receiver operating characteristic curve (AUC) value of 0.728. In the immunotherapy cohort, patients stratified as good responders showed a higher TRG0/1 rate (37/55, 67.3%) than poor response patients (18/65, 27.7%, <i>p</i> < 0.001) and had better overall survival (<i>p</i> = 0.001). In the external validation set, patients stratified using the clinical model as good responders also showed a higher TRG0/1 rate (14/18, 77.8%) than poor response patients (9/25, 36.0%, <i>p</i> = 0.012).</p><p><strong>Conclusion: </strong>The prediction model consisting of SMRA, NLR, and weight loss could help identify GC patients who respond well to chemotherapy plus PD-1 antibody.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1685592"},"PeriodicalIF":5.9,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12537701/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145344861","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}
Frontiers in ImmunologyPub Date : 2025-10-06eCollection Date: 2025-01-01DOI: 10.3389/fimmu.2025.1707327
Xiaopeng Chen, Zhiqi Yang, Minghao Li
{"title":"Correction: Molecular regulatory mechanisms and diagnostic potential of dendritic cell-derived exosomes in liver transplantation: from immune tolerance induction to translational challenges.","authors":"Xiaopeng Chen, Zhiqi Yang, Minghao Li","doi":"10.3389/fimmu.2025.1707327","DOIUrl":"https://doi.org/10.3389/fimmu.2025.1707327","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.3389/fimmu.2025.1657956.].</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1707327"},"PeriodicalIF":5.9,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12536260/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145344725","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}
Frontiers in ImmunologyPub Date : 2025-10-06eCollection Date: 2025-01-01DOI: 10.3389/fimmu.2025.1677358
Zahra Jamila Ikra, Qiutong Huang, Huiyang Yu, Gabrielle T Belz, Craig N Jenne, Nicolas Jacquelot
{"title":"Unspoken words: decoding the dialog between type 2 innate lymphoid cells and T cells.","authors":"Zahra Jamila Ikra, Qiutong Huang, Huiyang Yu, Gabrielle T Belz, Craig N Jenne, Nicolas Jacquelot","doi":"10.3389/fimmu.2025.1677358","DOIUrl":"10.3389/fimmu.2025.1677358","url":null,"abstract":"<p><p>Type 2 innate lymphoid cells (ILC2s) are critical mediators of type 2 immunity that play non-redundant context-dependent modulatory functions. Primarily associated with responses against helminths and allergens via the activation of a potent epithelial-ILC2 axis, a growing body of evidence also suggests that a crosstalk between ILC2 and T cells is equally important in maintaining tissue homeostasis. In barrier tissues and secondary lymphoid organs, ILC2s co-localize with T cells, forming hubs where bi-directional signals are exchanged. Here, we describe the diversity of functional interactions between ILC2s and T cells, detailing known contact-dependent and -independent mechanisms, including a relatively new and still poorly defined antigen-presenting function during inflammation. Understanding these complex interactions is necessary to fully elucidate how this specific crosstalk helps maintain tissue homeostasis and regulate inflammatory responses. Identifying the spatial and temporal specificities of these interactions will certainly open new avenues for future targeting of this axis to improve immune-mediated host protection.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1677358"},"PeriodicalIF":5.9,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12536036/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145344705","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}
Frontiers in ImmunologyPub Date : 2025-10-06eCollection Date: 2025-01-01DOI: 10.3389/fimmu.2025.1628872
Chelsey Skeete, Gabriel Sgambettera, Aldana D Gojanovich, Xianbao He, Daniel Bryant, Mengwei Yang, Shreya Banerjee, Andrés A Quiñones-Molina, Hisashi Akiyama, Gustavo Mostoslavsky, Andrew J Henderson, Suryaram Gummuluru
{"title":"Mu opioid receptor activation in microglia enhances HIV-1 infection and HIV-infection-induced inflammatory responses.","authors":"Chelsey Skeete, Gabriel Sgambettera, Aldana D Gojanovich, Xianbao He, Daniel Bryant, Mengwei Yang, Shreya Banerjee, Andrés A Quiñones-Molina, Hisashi Akiyama, Gustavo Mostoslavsky, Andrew J Henderson, Suryaram Gummuluru","doi":"10.3389/fimmu.2025.1628872","DOIUrl":"10.3389/fimmu.2025.1628872","url":null,"abstract":"<p><p>People living with HIV-1 (PWH) and chronically using opioids have elevated risks of developing HIV-associated neurological disorders (HAND) that are often correlated with persistent inflammation. Microglia, innate immune cells in the brain, are the principal HIV-1 reservoir in the central nervous system and regulate neuroinflammation. Our group previously showed that HIV-1 infection of induced pluripotent stem cell (iPSC)-derived microglia and viral intron-containing RNA (icRNA) expression triggers inflammatory responses. Microglia express μ opioid receptor, MOR, yet the immunomodulatory effects of opioids on HIV-1 infection in microglia are unclear. Here, we report that MOR activation impacts HIV-1 infection establishment and HIV-1-induced innate responses in microglia. Morphine pretreatment enhanced reverse transcription (RT), integration, viral transcription, and p24<sup>Gag</sup> secretion in HIV-1-infected iPSC-derived microglia, which was blocked by treatment with naloxone, a MOR antagonist. In contrast, morphine treatment did not impact HIV-1 infection in MOR-deficient monocyte-derived macrophages, although, induced exogenous expression of MOR in macrophages conferred morphine-mediated enhancement of HIV-1 infection. Interestingly, viral transcriptome analysis by digital-drop PCR revealed selective enhancement of HIV-1 icRNA expression in morphine-exposed iPSC-derived microglia, which correlated with enhanced HIV-1 icRNA-induced secretion of IP-10 in MOR+ cells. Further, PI3K inhibitor, wortmannin, blocked morphine-mediated enhancement of HIV-1 replication and HIV-1 icRNA-induced IP-10 secretion, suggesting that MOR signaling and HIV-1 icRNA expression synergistically activate the PI3K-Akt signaling pathway in microglia to exacerbate virus-induced inflammatory responses.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1628872"},"PeriodicalIF":5.9,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12536016/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145344816","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}
Frontiers in ImmunologyPub Date : 2025-10-06eCollection Date: 2025-01-01DOI: 10.3389/fimmu.2025.1581286
Mei Xia, Azra Blazevic, Huan Ning, Christopher S Eickhoff, Chad E Storer, Richard D Head, Jianguo Liu, Jessica Jarvela, David Stoeckel, Erin Rakey, Jan Tennant, Daniel L Miller, Kathleen R Holloway, Richard F Silver, Daniel F Hoft
{"title":"Th9 cells provide protective TB immunity.","authors":"Mei Xia, Azra Blazevic, Huan Ning, Christopher S Eickhoff, Chad E Storer, Richard D Head, Jianguo Liu, Jessica Jarvela, David Stoeckel, Erin Rakey, Jan Tennant, Daniel L Miller, Kathleen R Holloway, Richard F Silver, Daniel F Hoft","doi":"10.3389/fimmu.2025.1581286","DOIUrl":"10.3389/fimmu.2025.1581286","url":null,"abstract":"<p><strong>Introduction: </strong>CD4+ Th9 cells have been associated with inflammatory and allergic diseases. IL-9/Th9 can function as both positive and negative immune regulators, but their protective effects against <i>Mycobacterium tuberculosis</i>(Mtb) are unknown. We found that Th9 cells were associated with mycobacteria-specific T cell responses primed by latent tuberculosis infection and BCG vaccination.</p><p><strong>Methods: </strong>To study TB-specific Th9 protective effects, we generated Th9 cells from ESAT6-specific TCR transgenic mice and healthy human donors.</p><p><strong>Results: </strong>Both murine and human Th9 cells significantly inhibited intracellular mycobacterial growth. In both <i>in vitro</i> models, IL-9 neutralization strongly reduced Th9 protective effects, and IL-9 treatment alone inhibited intracellular mycobacteria. ESAT-6-specific Th9 and Th1 cells were adoptively transferred into naïve Rag1/2<sup>-/-</sup> recipients before aerosol Mtb infection. Th9 cells provided robust immunity as protective as Th1 cells, significantly reducing bacteria and pathologic changes post-infection. Differential persistence of Th9 vs. Th1 cell phenotypes was confirmed <i>in vivo</i>, and lung tissue qRT-PCR studies demonstrated the absence of IFN-γ responses in Th9-transferred mice, combined with unique expression of the Th9 specific markers IL-9, IL-10 and PU.1.</p><p><strong>Discussion: </strong>Th9 cells can provide important protection against Mtb infection, and should be targeted with future TB vaccine strategies. Furthermore, Th9 cells appear to utilize a novel protective mechanism independent from Th1-mediated protective responses.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1581286"},"PeriodicalIF":5.9,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12535965/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145344854","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":"Pan-cancer convergence of tumour-immune microenvironment motifs revealed by CyTOF and imaging mass cytometry.","authors":"Alexandre Vallée, Alexandre Drezet, Maxence Arutkin","doi":"10.3389/fimmu.2025.1672312","DOIUrl":"10.3389/fimmu.2025.1672312","url":null,"abstract":"<p><p>Mass cytometry (CyTOF) and Imaging Mass Cytometry (IMC) provide single-cell resolution for over 50 protein markers, enabling unprecedented exploration of tumour and immune heterogeneity. We conducted a scoping review of 61 original studies (inception-2025), spanning 17 cancer types, to map current applications, analytical strategies, and emerging biological insights. 46 studies used CyTOF alone, 12 employed IMC exclusively, and 3 combined both platforms. Median panel sizes were 33.5 markers for CyTOF and 33 for IMC. While lineage and immune checkpoint markers were universal, phospho-epitopes, metabolic enzymes, and stromal proteins appeared in more focused subsets. Most studies followed a three-step analytical workflow: (i) segmentation or gating, (ii) unsupervised clustering, and (iii) downstream spatial or functional analyses. CyTOF investigations frequently identified exhausted CD8<sup>+</sup> T-cell subsets (e.g., PD-1<sup>+</sup>TIM-3<sup>+</sup>CD39<sup>+</sup>), suppressive myeloid populations (e.g., CD163<sup>+</sup>HLA-DR<sup>-</sup> macrophages), and metabolically reprogrammed Tregs. IMC studies uncovered spatial patterns predictive of outcome, such as tertiary lymphoid structures (TLSs) and macrophage-T cell exclusion zones. Several studies proposed predictive immune signatures or integrated CyTOF with transcriptomic or spatial datasets. We identified five recurrent immunobiological motifs, CD8<sup>+</sup> T-cell bifurcation, CD38<sup>+</sup> TAM barriers, TLS maturity, CTLA-4<sup>+</sup> NK-cell signatures and metabolically defined niches, highlighting convergent axes of resistance and response. Bioinformatic pipelines converged around FlowSOM or PhenoGraph clustering, CITRUS or elastic-net feature selection, and increasingly, machine learning and agent-based spatial modelling. Collectively, CyTOF and IMC are redefining biomarker discovery, therapeutic stratification, and virtual trial design in oncology, establishing high-dimensional CyTOF as a cornerstone of next-generation precision cancer medicine.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1672312"},"PeriodicalIF":5.9,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12535963/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145344866","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}
Frontiers in ImmunologyPub Date : 2025-10-06eCollection Date: 2025-01-01DOI: 10.3389/fimmu.2025.1706172
Jinhwan Kim, Kelsey P Kubelick
{"title":"Editorial: Monitoring the immune/tumor microenvironment to improve cancer immunotherapy.","authors":"Jinhwan Kim, Kelsey P Kubelick","doi":"10.3389/fimmu.2025.1706172","DOIUrl":"10.3389/fimmu.2025.1706172","url":null,"abstract":"","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1706172"},"PeriodicalIF":5.9,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12535959/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145344693","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}
Frontiers in ImmunologyPub Date : 2025-10-06eCollection Date: 2025-01-01DOI: 10.3389/fimmu.2025.1633892
Alessia Lamolinara, Chiara Di Lisio, Julie A Hixon, Pasquale Simeone, Antonella De Cola, Maria D Falco, Thomas J Meyer, Alessio Ferrone, Domenico Genovesi, Paola Lanuti, Wenqing Li, Vincenzo De Laurenzi, Manuela Iezzi, Francesca B Aiello, Scott K Durum
{"title":"IL-7 promotes the formation of DNA double strand breaks and DNA repair in murine pro-B cells.","authors":"Alessia Lamolinara, Chiara Di Lisio, Julie A Hixon, Pasquale Simeone, Antonella De Cola, Maria D Falco, Thomas J Meyer, Alessio Ferrone, Domenico Genovesi, Paola Lanuti, Wenqing Li, Vincenzo De Laurenzi, Manuela Iezzi, Francesca B Aiello, Scott K Durum","doi":"10.3389/fimmu.2025.1633892","DOIUrl":"10.3389/fimmu.2025.1633892","url":null,"abstract":"<p><p>In pro-B cells, VDJ recombination at the immunoglobulin heavy chain locus is impaired. B cell progenitor recombination implies the formation of DNA double strand breaks (DSBs) by the RAG recombinase, which are subsequently repaired by specific mechanisms. We cultured primary murine pro-B cells with IL-7 to evaluate H2AX histone phosphorylation, a well-established marker of DSB formation (γ-H2AX foci) and the expression of proteins involved in DNA repair. Our results indicated that IL-7 upregulated the expression of several molecules involved in homologous recombination, the most accurate DSB repair mechanism. Quantitative analyses of γ-H2AX foci revealed that IL-7 significantly increased DSB formation in a time-dependent manner. Furthermore, γ-H2AX expression was altered in RAG2-deficient pro-B cells and absent in RAG1-deficient pro-B cells treated with IL-7, demonstrating the requirement of both RAG1 and RAG2 recombinase subunits. CD43 expression inversely correlates with the degree of cell differentiation and its level is often evaluated to assess the B lymphoid developmental stage. We observed that IL-7 upregulated CD43 expression and the percentage of large CD43/γ-H2AX double-positive cells, suggesting an effect on less differentiated, immature cells. Notably, we also found that IL-7 increased radiation-induced DSBs, while simultaneously supporting cell survival. This study uncovers novel effects of IL-7 on B cell differentiation, DSB formation, and DNA repair. It is well established that IL-7 promotes the proliferation and survival of acute lymphoblastic leukemia (ALL) cells. Our data suggest that drugs targeting IL-7 could improve ALL therapeutic protocols.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1633892"},"PeriodicalIF":5.9,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12535990/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145344785","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}
Frontiers in ImmunologyPub Date : 2025-10-06eCollection Date: 2025-01-01DOI: 10.3389/fimmu.2025.1626608
Carlo Cossa, Giulio Frigato, Massimo Lupo, Gabriele Mazzeo, Alex Moro, Francesco Patrucco, Reanna Wang, Andrea Doni, Piergiuseppe Colombo
{"title":"Predicting immune checkpoint inhibitors response via fluorescence lifetime imaging microscopy: a systematic review.","authors":"Carlo Cossa, Giulio Frigato, Massimo Lupo, Gabriele Mazzeo, Alex Moro, Francesco Patrucco, Reanna Wang, Andrea Doni, Piergiuseppe Colombo","doi":"10.3389/fimmu.2025.1626608","DOIUrl":"10.3389/fimmu.2025.1626608","url":null,"abstract":"<p><strong>Introduction: </strong>Fluorescence Lifetime Imaging Microscopy (FLIM) is an imaging technique that allows for the visualization of the cellular microenvironment by measuring the decay time of endogenous fluorescent molecules. Its advent has allowed the acquisition of information on previously undetectable aspects of the tissue environment, which also includes some mechanisms involving immune checkpoints. Understanding the level of interaction with their ligands is of paramount importance when stratifying patients for immunotherapy, as traditional methods such as immunohistochemistry (IHC) were found to be ineffective in predicting responders.</p><p><strong>Methods: </strong>This review analyzes the current literature on FLIM as a means of predicting targets' responsiveness to ICIs by examining the most relevant databases. Following PRISMA guidelines, we identified the relevant literature. The predefined objective of this review was to evaluate the potential of FLIM as a predictive biomarker of responsiveness to immune checkpoint inhibitors (ICIs). Eligibility criteria included original studies (clinical or preclinical) reporting on the use of FLIM to assess tumor or immune microenvironment in the context of ICI therapy. Reviews, case reports, editorials, and abstracts without full text were excluded.</p><p><strong>Results: </strong>Research suggests that interaction, not expression, is positively correlated with the effectiveness of ICI treatment. FLIM, in combination with FRET, allows for the quantification of the interactions within the tumor microenvironment.</p><p><strong>Discussion: </strong>The scope of the review is to assist researchers in further exploring this technology for possible applications and for future drug interaction studies.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1626608"},"PeriodicalIF":5.9,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12535979/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145344913","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}
Frontiers in ImmunologyPub Date : 2025-10-06eCollection Date: 2025-01-01DOI: 10.3389/fimmu.2025.1664371
Chih-Chao Chang, Ya Nan Liu, Zheng Xu, Elena-Rodica Vasilescu, Ping Li, Eric K Ho, Muyang Li, Syed A Husain, Govind Bhagat, Sumit Mohan, George Vlad, Nicole Suciu-Foca
{"title":"Development of potent HLA-A02:01-restricted peptide-based cytotoxic T-cells against SARS-CoV-2 infections in patients awaiting a kidney transplant.","authors":"Chih-Chao Chang, Ya Nan Liu, Zheng Xu, Elena-Rodica Vasilescu, Ping Li, Eric K Ho, Muyang Li, Syed A Husain, Govind Bhagat, Sumit Mohan, George Vlad, Nicole Suciu-Foca","doi":"10.3389/fimmu.2025.1664371","DOIUrl":"10.3389/fimmu.2025.1664371","url":null,"abstract":"<p><strong>Background: </strong>Controlling viral infections prior to solid organ transplantation is vital for successful engraftment and overall well-being of patients. One promising approach involves the deployment of viral antigen-specific cytotoxic T cells to eradicate viral pathogens. Although there have been attempts to develop anti-viral vaccines in the literature, the limited number of virus-specific cells which can be generated <i>in vitro</i> in the autologous system make it impracticable for autologous therapy.</p><p><strong>Methods: </strong>We developed a straightforward and scalable method for the <i>in vitro</i> expansion of SARS-CoV-2 Spike S1 peptide-specific cytotoxic CD8<sup>+</sup> T cells. This was achieved through combinatorial stimulation with S peptide-conjugated polystyrene microspheres in the presence of cytokines IL-2, IL-7, and IL-15 for 14 days.</p><p><strong>Results: </strong>Using A2/S<sub>269</sub>-specific tetramers as markers, we compared induction of S-specific CD8<sup>+</sup> T cells from patients awaiting kidney transplantation (n=67) with that of normal controls (n=65). We found that this method has the potential to achieve at least a 10-fold up to 200-fold increase in S-specific CD8<sup>+</sup> T cells in 34.3% of kidney transplant candidates and 36.9% of normal controls, respectively. These SARS-CoV-2 specific CD8<sup>+</sup> T cells released inflammatory cytokines, expressed effector-memory T cells markers, and killed target cells in a dose-dependent and antigen-specific manner.</p><p><strong>Conclusion: </strong>Our study demonstrates that viral antigen-specific cytotoxic CD8<sup>+</sup> T cells can be robustly enriched <i>in vitro</i> from peripheral blood mononuclear cells of both healthy individuals and patients with kidney diseases using peptide-conjugated microspheres. Our findings provide novel insights into a potential therapeutic approach, using autologous anti-viral CD8<sup>+</sup> T cells for transplant recipients/candidates.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1664371"},"PeriodicalIF":5.9,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12535972/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145344661","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}