Rheumatoid arthritis associated cytokines and therapeutics modulate immune checkpoint receptor expression on T cells.

Introduction: We investigated the impact of rheumatoid arthritis (RA) associated cytokines and standard of care (SOC) RA therapeutics on immune checkpoint receptor (IR) expression on T cells to gain insights to disease pathology and therapeutic avenues.

Methods: We assessed IR expression by flow cytometry on T cell receptor activated T cells cultured in the presence of exogenously added single cytokines or RA patient synovial fluid. We also assessed RA synovial fluid stimulated samples in the presence of various single cytokine neutralizing antibodies or SOC therapeutics, including glucocorticoids, TNF, IL-6 receptor and JAK inhibitors.

Enhancing the Generation of Eomes CD8 T Cells Augments the Efficacy of OX40- and CTLA-4-Targeted Immunotherapy.

CTLA-4 blockade in combination with an agonist OX40-specific monoclonal antibody synergizes to augment antitumor immunity through enhanced T-cell effector function, leading to increased survival in preclinical cancer models. We have shown previously that anti-OX40/anti-CTLA-4 combination therapy synergistically enhances the expression of Eomesodermin (Eomes) in CD8 T cells. Eomes is a critical transcription factor for the differentiation and memory function of CD8 T cells.

Immunological Complexity of the Prostate Cancer Microenvironment Influences the Response to Immunotherapy.

Prostate cancer is one of the most common cancers in men and a leading cause of cancer-related death. Recent advances in the treatment of advanced prostate cancer, including the use of more potent and selective inhibitors of the androgen signaling pathway, have provided significant clinical benefit for men with metastatic castration-resistant prostate cancer (mCRPC). However, most patients develop progressive lethal disease, highlighting the need for more effective treatments.

Overcoming Tumor-Induced Immune Suppression: From Relieving Inhibition to Providing Costimulation with T Cell Agonists.

Recent advancements in T-cell biology and antibody engineering have opened doors to significant improvements in cancer immunotherapy. Initial success with monoclonal antibodies targeting key receptors that inhibit T-cell function such as cytotoxic T lymphocyte antigen 4 (CTLA-4) and programmed death-ligand 1 (PD-1) have demonstrated the potency of this new class of therapy, highlighted by long-term complete responses for metastatic cancers once thought incurable. However, only a subset of patients responds to checkpoint blockade because of a multitude of factors, including an immunosuppressive tumor microenvironment and the mutational burden of the cancer.