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Pharmacological potentiation of monocyte-derived dendritic cell cancer immunotherapy

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Abstract

Dendritic cells have been at the forefront of cancer-immunotherapy research for over 2 decades. They elicited that attention by having an unprecedented capacity to mount T cells responses against tumors. However, the clinical use of DC-based vaccination against established malignancies has resulted in limited clinical benefits. Several factors are responsible for limiting the efficacy of DC-based immunotherapy, such as the harmful influence of the tumor microenvironment on DCs activity. New insights into the inner process of DC-mediated T cell activation have supported the development of new strategies that potentiate DCs-based therapies. Herein, we identify signaling cascades that have recently been targeted by small molecules and biologicals to promote the activation of monocyte-derived DCs and decrease their susceptibility to becoming tolerogenic. While Statins can markedly enhance antigen presentation, protein kinase inhibitors can be used to increase the expression of co-receptors and adhesion molecules. STAT3 and IDO can be modulated to limit the production of regulatory factors that work against differentiation and activation. The targeting of multiple pathways simultaneously has also been found to produce synergism and drastically enhance DCs activity. Some of these strategies have recently yielded positive results in clinical settings against established malignancies such as non-small cell lung cancer. The emergence of these approaches opens the door for a new generation of potent dendritic cell-based therapeutics to fight cancer.

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Acknowledgments

We thank Dr. Noriko Uetani for her help with the original figures. AP is a Canderel Studentship and FRSQ doctoral scholarship recipient. MLT is a Distinguished James McGill Professor and the holder of the J. and J.L. Levesque Chair in Cancer Research. This work was supported by a Canadian Institute of Health Research Foundation grant to MLT (CIHR FDN-159923), the Richard and Edith Strauss Canada Foundation, the Aclon Foundation and the FRQS Oncopole program.

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  1. Goodman Cancer Institute, McGill University, Montréal, Québec, Canada

    Alexandre Poirier & Michel L. Tremblay

  2. Department of Experimental Medicine, McGill University, Montréal, Québec, Canada

    Alexandre Poirier

  3. Department of Biochemistry, McGill University, Montréal, Québec, Canada

    Michel L. Tremblay

  4. Faculty of Medicine, McGill University, Montréal, Québec, Canada

    Michel L. Tremblay

  5. Rosalind and Morris Goodman Cancer Institute, McGill University, 1160 Pine Avenue West, Montréal, Québec, H3A 1A3, Canada

    Michel L. Tremblay

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AP and MLT had the idea for the article, AP performed the literature search, data analysis, and drafted the work. MLT critically revised the work and provided supervision. All authors reviewed the manuscript.

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Correspondence to Michel L. Tremblay.

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Poirier, A., Tremblay, M.L. Pharmacological potentiation of monocyte-derived dendritic cell cancer immunotherapy. Cancer Immunol Immunother 72, 1343–1353 (2023). https://doi.org/10.1007/s00262-022-03333-y

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