Page 53 - Hormel Institute Annual Report 2021-22

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A: Non-Activated
B: Activated
C: Activated + drug treated
Recent Publications:
• Puth, S.*, Verma, V.*, Hong, S. H., Tan, W., Lee, S. E., & Rhee, J. H. (2022). An all-in-one adjuvanted therapeutic cancer vaccine targeting dendritic cell cytosol induces long-lived tumor suppression through NLRC4 inflammasome activation. Biomaterials, 286, 121542.
• Sautès-Fridman, C., Dimberg, A., & Verma, V. (2022). Editorial: Tertiary Lymphoid Structures: From Basic Biology to Translational Impact in Cancer. Front Immunol, 13, 870862.
• Nandre, R.*, Verma, V.*, Gaur, P., Patil, V., Yang, X., Ramlaoui, Z., Shobaki, N., Andersen, M. H., Pedersen, A. W., Zocca, M. B., Mkrtichyan, M., Gupta, S., & Khleif, S. N. (2022). IDO Vaccine Ablates Immune-Suppressive Myeloid Populations and Enhances Antitumor Effects Independent of Tumor Cell IDO Status. Cancer Immunol Res, 10(5), 571-580.
• Verma, V., Jafarzadeh, N., Boi, S., Kundu, S., Jiang, Z., Fan, Y., Lopez, J., Nandre, R., Zeng, P., Alolaqi, F., Ahmad, S., Gaur, P., Barry, S. T., Valge- Archer, V. E., Smith, P. D., Banchereau, J., Mkrtichyan, M., Youngblood,
B., Rodriguez, P. C., Gupta, S., & Khleif, S. N. (2021). MEK inhibition reprograms CD8(+) T lymphocytes into memory stem cells with potent antitumor effects. Nat Immunol, 22(1), 53-66.
(*Equal contribution)
Figure shows the increased mitochondrial mass (green) in drug treated CD8 T cells (C) compared to naïve (A) or non-drug treated (B) cells, which is a measure of enhanced cell metabolism. As a result of enhanced metabolism these cells (C) will have higher capacity to kill the tumor cells.
enzyme IDO that is secreted by macrophages enhances the anti-tumor ability of effector T cells. In addition, we have developed the use of small molecule inhibitors as a viable option for reduction of immune suppression and enhance effector functions. Additionally, we are addressing the issue of immune exhaustion by blocking the checkpoints (PD1, CTLA4, TIM3) that do not allow full activation of lymphocytes.
Targeting metabolic perturbations for the enhancement of cancer immunotherapy.
Metabolic status of immune cells is extremely important for their effector functions. In the complex tumor microenvironment, cells must compete for the nutrients and because of high proliferation rates, tumor cells utilize most of glucose and other nutrients leaving the immune cells exhausted. By targeting various molecules involved in metabolic pathways, we are developing strategies to counter the tumor cell-induced metabolic desert that would be helpful in reversing the immune cell exhaustion, making the cells more responsive to immune therapies. In addition, we are developing the approaches to optimally combine metabolic targeting with the conventional checkpoint therapy for robust anti-tumor outcomes.
Lab research activities:
https://www.hi.umn.edu/research/research-sections/immunology-cancer- immunotherapy-and-immune-metabolism/
ORCID iD: https://orcid.org/0000-0001-8129-4140