Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1245478 | ENA |
REPOSITORIES: ENA
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Project description:Exercise-induced microbiota metabolite enhances CD8 T cell antitumor immunity promoting immunotherapy efficacy
| PRJNA1248760 | ENA
Project description:RIG-I is a pattern recognition receptor involved in innate immunity, but its role in adaptive immunity remains unclear. Here, we demonstrate that RIG-I is upregulated in tumor infiltrating CD8+ T cells, where it functions as an intracellular checkpoint to negatively regulate CD8+ T cell function and limit antitumor immunity. Mechanically, up-regulation of RIG-I in CD8+ T cells is induced by retinoic acid (RA), a metabolite of vitamin A in TME, and direct inhibits the AKT/glycolysis signaling pathway. In addition, deletion of RIG-I enhances the efficacy of adoptively transferred T cells against solid tumors and inhibition of RIG-I enhances the response to PD-1 blockade. Our findings identify RIG-I as an intracellular checkpoint and a potential target for alleviating inhibitory constraints on T cells in cancer immunotherapy, either alone or in combination with immune checkpoint blockade.
2023-04-25 | GSE230045 | GEO
Project description:Exercise improves immune checkpoint inhibitor (ICI) efficacy in cancers like melanoma, however, the mechanisms through which exercise mediates this antitumor effect remain obscure. Here we identify the gut microbiota as playing a previously unrecognized, critical role in how exercise improves ICI efficacy in preclinical melanoma. Our study demonstrates that exercise stimulates microbial one-carbon metabolism, increasing levels of the metabolite formate, which subsequently enhances Tc1-mediated ICI efficacy. We further establish that microbiota-derived formate is both sufficient and required to enhance Tc1 cell fate in vitro and promote tumor antigen-specific Tc1 immunity in vivo. Mechanistically, we identified the transcription factor nuclear factor erythroid 2-related factor-2 (Nrf2) as a crucial mediator of formate-driven Tc1 function enhancement in vitro and a key player in the exercise-mediated antitumor effect in vivo. Finally, we identify human microbiota-derived formate as a potential biomarker of enhanced Tc1-mediated antitumor immunity and support its functional role in driving melanoma suppression.
2025-07-23 | GSE294230 | GEO
Project description:In this project, we transfected MC38 cells with Flag-tagged Mbtps1 or vector control. After that, we performed immunoprecipitation–mass spectrometry analysis to search the interacting proteins of MBTPS1. In our study, We observed that the loss of membrane-bound transcription factor site-1 protease (MBTPS1) in tumor cells enhanced antitumor immunity and potentiated anti-PD-1 therapy. Mechanistic studies revealed that tumor cell-intrinsic MBTPS1 competed with USP13 for binding to STAT1, thereby disrupting USP13-dependent deubiquitination and stabilization of STAT1. MBTPS1 deficiency induced CXCR3+ CD8+ T cell infiltration by upregulating STAT1-transcribed chemokines including CXCL9, CXCL10 and CXCL11. Notably, the regulatory role of MBTPS1 in antitumor immunity operates independently of its classic function in cleaving membrane-bound transcription factors. Collectively, our results provide a theoretical basis for MBTPS1 as a potential immunotherapy target and also as a predictor of immunotherapy efficacy.
2025-04-11 | PXD053978 | Pride
Project description:<p>B7H3 (CD276), a key immune checkpoint molecule that is overexpressed in tumors, plays a central role in cancer progression, making it a highly promising and specific therapeutic target. Here, we discovered that the cellular metabolite palmitic acid contributes to the development of an immunosuppressive microenvironment in colorectal cancer by triggering the palmitoylation of B7H3. Mechanistically, the palmitoyltransferase ZDHHC24 catalyzes the palmitoylation of B7H3 at Cys496, preventing its binding to the autophagy adaptor protein SQSTM1/p62 and inhibiting autophagic degradation. Using spectral flow techniques, we demonstrated that the mutation of this palmitoylation site restored CD8+ T cell antitumor activity. Additionally, CD8+ T cells also showed enhanced antitumor activity in a Zdhhc24-deficient colitis-associated colorectal (CAC) carcinogenesis mouse model. Furthermore, we developed a small-molecule peptide that enhances CD8+ T cell function by blocking the interaction between ZDHHC24 and B7H3, which works synergistically with anti-PD-1 therapy. In conclusion, our study revealed that B7H3 C496 palmitoylation is a critical immunosuppressive factor in colorectal cancer and represents a potential target for malignant immunotherapy.</p>
2025-12-03 | MTBLS12300 | MetaboLights
Project description:Conventional chemotherapy achieves clinical efficacy beyond its cytotoxic effects by reactivating immune surveillance. However, whether chemotherapy promotes immune evasion by remodeling the tumor microenvironment (TME) remains largely unexplored. Here, we integrate cross-species single-cell and spatial transcriptomics to explore how chemotherapy reprograms immune cell dynamics and plasticity. Our findings reveal a central role for chemotherapy-educated, liver-resident Kupffer cells (KCs) in promoting immune tolerance and chemoresistance in liver metastases. These reprogrammed KCs, characterized by leptin receptor expression (LEPR+), originate from preexisting KCs and are differentiated via STING-ID1 signaling triggered by cGAMP released from chemotherapy-treated tumor cells. Unlike conventional KCs, LEPR+ KCs infiltrate tumors and engage in MerTK-dependent efferocytosis, which diminishes chemotherapy-induced immunogenic cell death (ICD) and suppresses antitumor immunity. Notably, targeting LEPR+ KCs enhances tumor immunogenicity and strengthens antitumor T-cell responses. Our study demonstrates that therapy-induced KC differentiation fosters immune evasion and suggests combining efferocytosis inhibitors with immunotherapy to overcome chemoresistance.
2025-12-29 | GSE285990 | GEO
Project description:Conventional chemotherapy achieves clinical efficacy beyond its cytotoxic effects by reactivating immune surveillance. However, whether chemotherapy promotes immune evasion by remodeling the tumor microenvironment (TME) remains largely unexplored. Here, we integrate cross-species single-cell and spatial transcriptomics to explore how chemotherapy reprograms immune cell dynamics and plasticity. Our findings reveal a central role for chemotherapy-educated, liver-resident Kupffer cells (KCs) in promoting immune tolerance and chemoresistance in liver metastases. These reprogrammed KCs, characterized by leptin receptor expression (LEPR+), originate from preexisting KCs and are differentiated via STING-ID1 signaling triggered by cGAMP released from chemotherapy-treated tumor cells. Unlike conventional KCs, LEPR+ KCs infiltrate tumors and engage in MerTK-dependent efferocytosis, which diminishes chemotherapy-induced immunogenic cell death (ICD) and suppresses antitumor immunity. Notably, targeting LEPR+ KCs enhances tumor immunogenicity and strengthens antitumor T-cell responses. Our study demonstrates that therapy-induced KC differentiation fosters immune evasion and suggests combining efferocytosis inhibitors with immunotherapy to overcome chemoresistance.
2025-12-29 | GSE285989 | GEO
Project description:Analysis of the effect of cyclophosphamide on peripheral blood leukocyte gene expression. Certain chemotherapeutic drugs such as cyclophosphamide can enhance the antitumor efficacy of immunotherapy because of their capacity to modulate innate and adaptive immunity. Indeed, it has been argued that this capacity may be more significant to chemotherapeutic efficacy in general than is presently appreciated. To gain insights into the core mechanisms of chemoimmunotherapy, we methodically profiled the effects of cyclophosphamide on gene expression in bone marrow, spleen and peripheral blood, and on cytokine expression in plasma and bone marrow of tumor-bearing mice. Gene and protein expression were modulated early and transiently by cyclophosphamide, leading to upregulation of a variety of immunomodulatory factors, including danger signals, pattern recognition receptors, inflammatory mediators, growth factors, cytokines, chemokines and chemokine receptors. These factors are involved in sensing cyclophosphamide myelotoxicity and activating repair mechanisms, which, in turn, stimulate immunoactivation events that promote efficacy. In particular, cyclophosphamide induced a T helper 17 (Th17)-related gene signature associated with an increase in Th17, Th1 and activated CD25+CD4+Foxp3- T lymphocytes and a slight recovery of regulatory T-cells. By analyzing gene and protein expression kinetics and their relationship to the antitumor efficacy of different therapeutic schedules of combination, we determined that optimal timing for performing adoptive immunotherapy is approximately 1 day after cyclophosphamide treatment. Together, our findings highlight factors that may propel the efficacy of chemoimmunotherapy, offering a mechanistic glimpse of the important immune modulatory effects of cyclophosphamide Four-condition experiment, Untreated mice - Cyclophosphamide-treated mice 1 day - Cyclophosphamide-treated mice 2 days - Cyclophosphamide-treated mice 5 days. Biological replicates: 4, controls: 4, independently harvested. Two replicates per array.
2011-04-27 | E-GEOD-27422 | biostudies-arrayexpress
Project description:Analysis the effect of cyclophosphamide on splenocytes gene expression. Certain chemotherapeutic drugs such as cyclophosphamide can enhance the antitumor efficacy of immunotherapy because of their capacity to modulate innate and adaptive immunity. Indeed, it has been argued that this capacity may be more significant to chemotherapeutic efficacy in general than is presently appreciated. To gain insights into the core mechanisms of chemoimmunotherapy, we methodically profiled the effects of cyclophosphamide on gene expression in bone marrow, spleen and peripheral blood, and on cytokine expression in plasma and bone marrow of tumor-bearing mice. Gene and protein expression were modulated early and transiently by cyclophosphamide, leading to upregulation of a variety of immunomodulatory factors, including danger signals, pattern recognition receptors, inflammatory mediators, growth factors, cytokines, chemokines and chemokine receptors. These factors are involved in sensing cyclophosphamide myelotoxicity and activating repair mechanisms, which, in turn, stimulate immunoactivation events that promote efficacy. In particular, cyclophosphamide induced a T helper 17 (Th17)-related gene signature associated with an increase in Th17, Th1 and activated CD25+CD4+Foxp3- T lymphocytes and a slight recovery of regulatory T-cells. By analyzing gene and protein expression kinetics and their relationship to the antitumor efficacy of different therapeutic schedules of combination, we determined that optimal timing for performing adoptive immunotherapy is approximately 1 day after cyclophosphamide treatment. Together, our findings highlight factors that may propel the efficacy of chemoimmunotherapy, offering a mechanistic glimpse of the important immune modulatory effects of cyclophosphamide Four-condition experiment, Untreated mice - Cyclophosphamide-treated mice 1 day - Cyclophosphamide-treated mice 2 days - Cyclophosphamide-treated mice 5 days. Biological replicates: 5, controls: 5, independently harvested. Two replicates per array.
2011-04-27 | E-GEOD-27423 | biostudies-arrayexpress
Project description:Analysis the effect of cyclophosphamide on bone marrow gene expression. Certain chemotherapeutic drugs such as cyclophosphamide can enhance the antitumor efficacy of immunotherapy because of their capacity to modulate innate and adaptive immunity. Indeed, it has been argued that this capacity may be more significant to chemotherapeutic efficacy in general than is presently appreciated. To gain insights into the core mechanisms of chemoimmunotherapy, we methodically profiled the effects of cyclophosphamide on gene expression in bone marrow, spleen and peripheral blood, and on cytokine expression in plasma and bone marrow of tumor-bearing mice. Gene and protein expression were modulated early and transiently by cyclophosphamide, leading to upregulation of a variety of immunomodulatory factors, including danger signals, pattern recognition receptors, inflammatory mediators, growth factors, cytokines, chemokines and chemokine receptors. These factors are involved in sensing cyclophosphamide myelotoxicity and activating repair mechanisms, which, in turn, stimulate immunoactivation events that promote efficacy. In particular, cyclophosphamide induced a T helper 17 (Th17)-related gene signature associated with an increase in Th17, Th1 and activated CD25+CD4+Foxp3- T lymphocytes and a slight recovery of regulatory T-cells. By analyzing gene and protein expression kinetics and their relationship to the antitumor efficacy of different therapeutic schedules of combination, we determined that optimal timing for performing adoptive immunotherapy is approximately 1 day after cyclophosphamide treatment. Together, our findings highlight factors that may propel the efficacy of chemoimmunotherapy, offering a mechanistic glimpse of the important immune modulatory effects of cyclophosphamide Four-condition experiment, Untreated mice - Cyclophosphamide-treated mice 1 day - Cyclophosphamide-treated mice 2 days - Cyclophosphamide-treated mice 5 days. Biological replicates: 5, controls: 5, independently harvested. Two replicates per array.
2011-04-27 | E-GEOD-27421 | biostudies-arrayexpress