Abstract
Advances in immuno-oncology (IO) are making immunotherapy a powerful tool for cancer treatment. With the discovery of an increasing number of IO targets, many herbs or ingredients from traditional Chinese medicine (TCM) have shown immunomodulatory function and antitumor effects via targeting the immune system. However, knowledge of underlying mechanisms is limited due to the complexity of TCM, which has multiple ingredients acting on multiple targets. To address this issue, we present TCMIO, a comprehensive database of Traditional Chinese Medicine on Immuno-Oncology, which can be used to explore the molecular mechanisms of TCM in modulating the cancer immune microenvironment. Over 120,000 small molecules against 400 IO targets were extracted from public databases and the literature. These ligands were further mapped to the chemical ingredients of TCM to identify herbs that interact with the IO targets. Furthermore, we applied a network inference-based approach to identify the potential IO targets of natural products in TCM. All of these data, along with cheminformatics and bioinformatics tools, were integrated into the publicly accessible database. Chemical structure mining tools are provided to explore the chemical ingredients and ligands against IO targets. Herb–ingredient–target networks can be generated online, and pathway enrichment analysis for TCM or prescription is available. This database is functional for chemical ingredient structure mining and network analysis for TCM. We believe that this database provides a comprehensive resource for further research on the exploration of the mechanisms of TCM in cancer immunity and TCM-inspired identification of novel drug leads for cancer immunotherapy. TCMIO can be publicly accessed at http://tcmio.xielab.net.
Highlights
The relationship between the human immune system and cancer can be traced back to 150 years ago, when Rudolf Virchow observed immune infiltration in human tumors and proposed the concept of mobilizing the immune system against cancer (Balkwill and Mantovani, 2001)
Small molecules have shown great potential to stimulate the immune system to respond to various cancers
Used traditional herbs have displayed immunomodulatory functions and extensive antitumor effects, which indicates that exploring the relations of traditional herbs and immuno-oncology would expand our understanding of the mechanism of action (MOA) of herbs and accelerate traditional medicine-inspired natural product drug discovery for cancer treatment
Summary
The relationship between the human immune system and cancer can be traced back to 150 years ago, when Rudolf Virchow observed immune infiltration in human tumors and proposed the concept of mobilizing the immune system against cancer (Balkwill and Mantovani, 2001). The milestone for cancer immunotherapy came with the identification of immune checkpoints, which control Tcell immune responses through on and off switches (Sharma and Allison, 2015). The expression of checkpoint proteins can be dysregulated within the tumor microenvironment, an important factor in immune resistance (Hoos, 2016). In 2011, the first checkpoint inhibitor, ipilimumab, an anti-CTLA4 antibody developed by BristolMyers Squibb (BMS), was approved for treatment of melanoma (O’Day et al, 2010). This marked the beginning of the cancer immunotherapy revolution and changed the paradigm of anti-cancer drug development. Various immunotherapies have been approved, and these new therapies have quickly become the standard of care for many cancer types (Pardoll, 2012)
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