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Exploring innate immunity in cancer immunotherapy: opportunities and challenges

Cellular & Molecular Immunology volume 18, pages 1607–1609 (2021)Cite this article

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The recognition of the important role of cancer immunity in tumors has led to the introduction of immunotherapeutic strategies. Most of the immunomodulatory approaches currently being developed engage the adaptive immune system. The clinical approval of checkpoint inhibitors and chimeric antigen receptor (CAR) T-cell therapy has led to considerable success in treating hematologic malignancies.1,2,3,4 However, for the majority of patients with solid tumors, little or no progress has been seen. The efficacy of immunotherapies is limited by the complexities of a diverse set of immune cells and interactions between tumor cells and all other cells in the local microenvironment of solid tumors. A large proportion of immune cells in and around solid tumors derive from the innate arm of the immune system, and using these innate cells against tumors offers an alternative immunotherapeutic option, while current strategies mainly focus on the adaptive arm of the immune system.5 In a recent issue of Cell research, Lv et al.6 discovered that Mn2+ played a critical role in the innate immune sensing of tumors, as Mn-insufficient mice poorly controlled tumor growth and metastasis. Mechanistically, Mn2+ promoted dendritic cell (DC) and macrophage maturation and tumor-specific antigen presentation, augmented CD8+ T-cell differentiation and activation and NK cell activation, and increased memory CD8+ T cells in a cyclic-AMP synthase (cGAS)-stimulator of interferon genes (STING)-dependent manner, uncovering a critical role of Mn in bridging innate and adaptive immunity for tumor surveillance.

The main components of the innate immune system involve various types of cells of the myeloid lineage, including DCs, monocytes, and macrophages, all of which function as professional antigen-presenting cells (APCs), and innate lymphoid cells, such as natural killer (NK) cells, rely on germline-encoded pattern-recognition receptors (PRRs) and other cell-surface receptors to rapidly detect microbial proteins or membranous molecules on tumor cells to orchestrate downstream inflammatory reactions.7 These cells initiate adaptive immune responses while mounting their own effector responses, such as macrophage phagocytosis and the natural cytotoxicity of NK cells.7,8 Integral to this bridging of innate and adaptive immunity is the ability of APCs to engulf tumor cells via phagocytosis, a cellular process involving target cell recognition, cellular engulfment, and lysosomal digestion that is regulated by receptor–ligand interactions between the target cell and the phagocyte.9

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Acknowledgements

This work was supported by funds from the National Natural Science Foundation of China (Nos. 31991171, 81830002, and 31870873 to W.D.H.).

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  1. Department of Oncology, the First Affiliated Hospital of Anhui Medical University, Hefei, China

    Xiaolei Li, Hanren Dai & Hua Wang

  2. Department of Biotherapy, the First Medical Center, Chinese PLA General Hospital, Beijing, China

    Weidong Han

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Correspondence to Hua Wang or Weidong Han.

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Li, X., Dai, H., Wang, H. et al. Exploring innate immunity in cancer immunotherapy: opportunities and challenges. Cell Mol Immunol 18, 1607–1609 (2021). https://doi.org/10.1038/s41423-021-00679-8

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