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Bioactive Lipid (BAL)-Based Therapeutic Approach to Cancer That Enhances Antitumor Action and Ameliorates Cytokine Release Syndrome of Immune Checkpoint Inhibitors

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Molecular Biochemical Aspects of Cancer

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Abstract

It is the aim of cancer therapy to selectively kill tumor cells with few or no side effects. But current therapeutic approaches such as surgery, radiotherapy, and chemotherapy including immune checkpoint inhibitors (ICI) are associated with mild to moderate to severe side effects that are considered to be responsible for significant morbidity and mortality to patients with cancer. The recently discovered and employed ICI therapy though produced significant remission in not more than 20–30% of the patients is capable of inducing severe side effects due to excess production of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α). It is paradoxical that appropriate amounts of IL-6 and TNF-α are needed to induce apoptosis of tumor cells. Hence, it is important to device newer methods of eliminating rather selectively tumor cells but at the same time prevent or eliminate or reduce cytokine storm-induced side effects. IL-6 and TNF-α induce the release of polyunsaturated fatty acids (PUFAs), especially GLA, DGLA, AA, EPA, and DHA, from the cell membrane phospholipids by activating phospholipases. Previously we and others showed that PUFAs induce apoptosis/ferroptosis/necrosis and other forms of tumor cell death and at the same time are capable of suppressing the release of excess IL-6 and TNF-α. NK cells, TILs (tumor-infiltrating cells), and γδ T cells release toxic granules (also called as cytolytic granules) that contain unsaturated fatty acids. Thus, PUFAs seem to be a universal component of cytolytic granules and are responsible for the cytotoxic action of NK cells, TILs, and γδ T cells especially against tumor cells. Hence, it is hypothesized that a combination of ICI/TILs/NK cells/γδ T cells and PUFAs is likely to form a novel, reliable, and robust method of inducing apoptosis of tumor cells with few side effects.

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Authors and Affiliations

  1. BioScience Research Centre and Department of Medicine, GVP Medical College and Hospital, Visakhapatnam, India

    Undurti N. Das

  2. UND Life Sciences, Battle Ground, WA, USA

    Undurti N. Das

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Das, U.N. (2020). Bioactive Lipid (BAL)-Based Therapeutic Approach to Cancer That Enhances Antitumor Action and Ameliorates Cytokine Release Syndrome of Immune Checkpoint Inhibitors. In: Molecular Biochemical Aspects of Cancer. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-0741-1_6

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