Page 54 - Hormel Report 2023

Vivek Verma, PhD
“Enhancing the efficacy of cancer
immunotherapy in solid tumors .”
Vivek Verma
54 | THE HORMEL INSTITUTE // UNIVERSITY OF MINNESOTA Cancer Immunotherapy, Immunology
and Immune Metabolism
ASSISTANT PROFESSOR
The Verma Lab is interested in under- standing the mechanisms that limit the effectiveness of cancer immunotherapy
against solid tumors. This is done by studying immunometabolomics and immune regulatory mechanisms in solid tumors. Solid cancers, because of their highly heterogeneous and complex nature, have factors such as regulatory T cells (Tregs), myeloid-derived suppressive cells (MDSCs), or checkpoint molecules (PD1, PD-L1, CTLA4, LAG3) that help them to either suppress the activated immune cells or prevent the acti- vation of the cells. Using multiomic approaches, we study these mechanisms and tend to develop cell-based and molecular targeting strategies for optimum therapeutic outcomes.
Multi-Pronged Approach to Tackling Therapy Resistance in Solid Tumors
1) We are looking at the immune exhaustion mechanisms that render the anti-tumor immune cells ineffective against solid tumors. Since mitochondria are an integral part of cell energy machinery, in one project using pharmacologi- cal interventions, we are looking to enhance the mitochondrial architecture and metabolism.
2) Tumor cell metabolism and the mode of substrate utilization for energy generation plays an extremely important role in deciding the suppressive tumor microenvironment. In one of the projects, we are working to alter the tumor cell metabolism so that suppressive
metabolites such as lactic acid and succinate can be reduced. Through this project we anticipate developing methods to boost the impact of cancer immunotherapy.
3) CAR-T cells are a new form of cancer immunotherapy in which host’s own immune cells are genetically modified to seek out and kill the tumor cells. CAR-T cells have worked wonderfully well against liquid tumors such as myelomas and leukemias. However, their therapeutic efficacy against solid tumors is severely limited. Our lab is actively looking at methods to enhance the anti-tumor efficacy of CAR-T cells against solid tumors such as melanoma and colon cancer. In one project we are investigating the effects of epigenetic regulation of CAR-T cells and its impact on their anti-tumor potential.
4) Host factors such as gut microbiome has been found to play a significant role in therapy outcomes in cancer patients. Our lab is interested in learning the underlying mechanisms through which the gut microbiome and its derived factors affect the efficacy of CAR-T cells and immune checkpoint blockade therapies.
ORCID iD: https://orcid.org/0000-0001-8129-4140