Natural Products Modulate the Sensitivity of Cancer to Anti-PD-1 Based Immunotherapy

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About this Research Topic

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Background

As a promising therapy strategy, immunotherapy has achieved tremendous clinical success over other cancer treatments. Immune checkpoint blockade (ICB), such as anti-PD-1 and PD-L1 drug, is emerging as front-line immunotherapy for several types of cancer, which block the association between PD-1 and PD-L1, effectively restore the growth and activation of T cells to enhance anti-tumor immunity, and prevent the progression of a variety of cancers, including lung cancer, melanoma, and colorectal cancer, etc. However, de-novo and acquired resistance are still seen in a large proportion of patients. A combination of cancer immunotherapy together with other anticancer drugs is being vigorously investigated and developed to maximize the therapeutic index and improve the responses to PD-1/PD-L1 based immunotherapy.

Natural sources have inspired numerous drug discovery efforts by providing potential bioactive constituents or leading components in drug development. Most clinically approved anti-cancer agents are either directly isolated from natural sources or modified from natural products. Due to being extracted from living organisms such as plants or animals, natural products are considered attractive agents with high bio-activity and low adverse effects. In addition to the anti-cancer activity by targeting tumor cells, the regulatory effects of natural products on the immune system are notable, therefore, their roles in cancer immunotherapy have gained more and more attention.

This Research Topic focuses on the studies of natural products that improve the response to immunotherapy and potential combination therapy strategies. The natural products should be pure compounds with identified structure and verified purity.

The Research Topic includes the following sub-topics, but are not limited to
• Potent natural products and the related combination strategy to overcome the resistance to cancer immunotherapy
• Target cells and molecules to mediate the sensitizing effect of natural products
• Methodologies and analytical systems to screen, identify and optimize immunotherapy sensitization drugs from natural products
• Database or web-based resources about natural products and immunotherapy
• Research progress of natural products to enhance tumor immunity and immunotherapy

Note: As many anticancer drugs working as cytotoxic compounds have non-selective effects annihilating their potential therapeutic benefits, manuscripts are advised to provide evidence of a significant selectivity towards cancer cells (vs. healthy cells). Specifically, if the studied anticancer drug or modality does not target an oncogenic pathway, the authors should make every effort possible to prove that the cytotoxic or cytostatic effects they have identified exhibit selectivity for cancer cells (ideally 1 log difference in EC50 or IC50) vs. non-malignant cells (eg, fibroblasts or primary culture of cells).

The authors should also demonstrate the applicability of their anticancer modalities on a minimum of two well-authenticated cancer cell lines (ideally originating from distinct organs/tissues). The utilization of in vivo models must also be supported by such evidence.

In addition, for manuscripts dealing with plant extracts or other natural sub-stances/compounds, the composition and the stability of the study material must be described in sufficient detail. In particular, for extracts, chromato-grams with characterization of the dominating compound(s) are requested. The level of purity must be proven and included.

Keywords: Natural products, immunotherapy, anti-PD-1/PD-L1, sensitivity, resistance

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