A5005147526- Cancer Immunotherapy and Biomarkers
- Immune cells in cancer
- CAR-T cell therapy research
- Immunotherapy and Immune Responses
- Immune Response and Inflammation
- Chemokine receptors and signaling
- Cytokine Signaling Pathways and Interactions
- vaccines and immunoinformatics approaches
- Monoclonal and Polyclonal Antibodies Research
- Inflammatory mediators and NSAID effects
- Advanced Breast Cancer Therapies
- Atherosclerosis and Cardiovascular Diseases
- T-cell and B-cell Immunology
Revolution Medicines (United States)
2024-2025
The University of Texas MD Anderson Cancer Center
2022-2024
The University of Texas Health Science Center at Houston
2022
Abstract Immune checkpoint therapy (ICT) using antibody blockade of programmed cell death protein 1 (PD-1) or cytotoxic T-lymphocyte-associated 4 (CTLA-4) can provoke T cell–dependent antitumor activity that generates durable clinical responses in some patients. The epigenetic and transcriptional features cells require for efficacious ICT remain to be fully elucidated. Herein, we report anti–PD-1 anti–CTLA-4 induce upregulation the transcription factor BHLHE40 tumor antigen–specific CD8+...
Abstract Colorectal cancer (CRC) is the third most commonly diagnosed in United States. About 40% of colorectal cancers have mutations KRAS, with KRAS G12D representing largest population. Targeted therapies, as well immune checkpoint inhibitor limited efficacy monotherapies for patients microsatellite stable (MSS) CRC. However, recent clinical evidence BRAF mutant MSS CRC showed that inhibitors combination MEK or EGFR and anti-PD-1 resulted significantly longer overall survival a higher...
Abstract Oncogenic RAS promotes carcinogenesis by sustaining cell proliferation and orchestrating immune escape. We others have shown that inhibition combined with checkpoint blockade (ICB) prolongs durability of response in immunogenic, RAS-driven preclinical models. Clinical data most patients treated KRAS G12C(OFF) inhibitors develop resistance through reactivation the pathway. previously demonstrated combination a RAS(ON) G12C-selective inhibitor multi-selective can overcome mechanisms...
Abstract Human leukocyte antigen class I (HLA-I) molecules bind and present peptides at the cell surface to facilitate induction of appropriate CD8+ T cell-mediated immune responses pathogen- self-derived proteins. The HLA-I peptide-binding cleft contains dominant anchor sites in B F pockets that interact primarily with amino acids peptide position 2 C-terminus, respectively. Nonpocket peptide–HLA interactions also contribute binding stability, but these secondary are thought be unique...
Abstract Mutant KRAS is present in more than 80% pancreatic cancer, promotes cancer cell survival, and protects cells from immune recognition attack. We have shown that inhibitors of the active state RAS (RAS(ON)) promote neoantigen synergize with immunotherapy preclinical immunogenic models. 1 evaluated impact RMC-6236, an investigational RASMULTI(ON) inhibitor on anti-tumor activity tumor microenvironment (TME) remodeling two congenic KRASG12D/+ GEMM-derived PDAC models resistant to...
Abstract T cell-dependent anti-tumor activity unleashed by immunotherapies such as immune checkpoint therapy (ICT) can generate durable clinical responses. However, not all patients benefit, and epigenetic transcriptional features required cells for effective ICT remain to be fully established. We previously documented that the transcription factor Bhlhe40 is upregulated in tumor specific CD4 CD8 preclinical models. validated relevance of this ablating both CD8-T which rendered αPD-1 or...
<h3>Background</h3> We previously documented that the transcription factor Bhlhe40 is upregulated by immune checkpoint therapy (ICT) in tumor specific CD4 and CD8 T cells preclinical models. validated relevance of this ablating both cells, which rendered αPD-1 or αCTLA-4 ICT ineffective models normally responsive to ICT. However, mechanisms underlying how regulates cell function context different ICTs yet be fully delineated. <h3>Methods</h3> used <i>CD4-Cre Bhlhe40<sup>f/f</sup></i>...
Supplementary Figure from BHLHE40 Regulates the T-Cell Effector Function Required for Tumor Microenvironment Remodeling and Immune Checkpoint Therapy Efficacy
<div>Abstract<p>Immune checkpoint therapy (ICT) using antibody blockade of programmed cell death protein 1 (PD-1) or cytotoxic T-lymphocyte-associated 4 (CTLA-4) can provoke T cell–dependent antitumor activity that generates durable clinical responses in some patients. The epigenetic and transcriptional features cells require for efficacious ICT remain to be fully elucidated. Herein, we report anti–PD-1 anti–CTLA-4 induce upregulation the transcription factor BHLHE40 tumor...
Supplementary Figure from BHLHE40 Regulates the T-Cell Effector Function Required for Tumor Microenvironment Remodeling and Immune Checkpoint Therapy Efficacy
<div>Abstract<p>Immune checkpoint therapy (ICT) using antibody blockade of programmed cell death protein 1 (PD-1) or cytotoxic T-lymphocyte-associated 4 (CTLA-4) can provoke T cell–dependent antitumor activity that generates durable clinical responses in some patients. The epigenetic and transcriptional features cells require for efficacious ICT remain to be fully elucidated. Herein, we report anti–PD-1 anti–CTLA-4 induce upregulation the transcription factor BHLHE40 tumor...
Abstract The success of immune checkpoint therapy (ICT) in generating durable clinical responses is remarkable but not all cancer patients respond for reasons that are incompletely understood. In our previous studies to ICT the mouse T3 sarcoma model, we found strong upregulation BHLHE40 transcription factor a number cell populations. It was particularly prominent tumor antigen-specific CD8+ and CD4+ T cells, which crucial ICT-induced rejection elimination. We used global cell-type specific...
Abstract Immune checkpoint therapy (ICT) (e.g. anti-CTLA-4, anti-PD-1) enables durable T-cell dependent anti-tumor immunity in patients with solid tumors. Since not all respond to ICT, this work aims at developing a more in-depth understanding of responses MHC class I (MHC-I) and II (MHC-II) tumor antigens that occur as consequence aberrant expression non-mutant or driver passenger mutations form neoantigens. We used poorly immunogenic Brafv600e Pten−/−Cdkn2a−/− YUMM1.7 (Y1.7) murine...