Manisha Singh
Assistant Professor
The University of Texas MD Anderson Cancer Center at Houston
Department of Immunology
My research centers on overcoming resistance to cancer immunotherapy, with a focus on colorectal cancer (CRC), pancreatic ductal adenocarcinoma (PDAC), and melanoma. A core theme of my work is understanding how the tumor microenvironment (TME), inflammatory cytokines, and immune cell plasticity contribute to treatment failure.
A significant area of my research involves CD40 agonist-based immunotherapy. CD40 is a key co-stimulatory molecule that activates antigen-presenting cells and enhances T cell priming. I have shown that CD40 agonists can reprogram the TME to support robust anti-tumor immunity, especially when combined with immune checkpoint inhibitors or small-molecule therapies. My studies have demonstrated that CD40 agonist efficacy is driven by CD8+ T cells and can overcome tumor-induced immune suppression, even in poorly immunogenic tumors. I also investigate mechanisms of toxicity, such as CD40-induced liver inflammation, and strategies to mitigate adverse effects through combination therapies or selective immune modulation.
Complementing this work, I explore how inflammatory signaling, particularly IL-1 and IL-6 pathways, further suppresses immunity and promotes resistance. My findings on IL-1α- driven immune evasion have led to the development of IL-1R1 blockade strategies now being advanced for clinical translation.
Using syngeneic and humanized mouse models, patient-derived tissues, and multiomic analyses, my research integrates fundamental immunology with translational goals. Ongoing studies also address the roles of fibroblasts, complement activation, and microbial factors in CRC. Ultimately, I aim to develop innovative, mechanism-based immunotherapies to improve outcomes in treatment-refractory cancers.
Education & Training
PhD, Sanjay Gandhi Post Graduate Institute of Medical Sciences, 2005