Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Comment
  • Published:

Exploring innate immunity in cancer immunotherapy: opportunities and challenges

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

Subjects

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

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1

References

  1. Lim, W. A. & June, C. H. The principles of engineering immune cells to treat cancer. Cell 168, 724–740 (2017).

    Article  CAS  Google Scholar 

  2. Sharma, P. & Allison, J. P. The future of immune checkpoint therapy. Science 348, 56–61 (2015).

    Article  CAS  Google Scholar 

  3. Li, X., Song, W., Shao, C., Shi, Y. & Han, W. Emerging predictors of the response to the blockade of immune checkpoints in cancer therapy. Cell Mol. Immunol. 16, 28–39 (2019).

    Article  CAS  Google Scholar 

  4. Wei, J. et al. Clinical development of CAR T cell therapy in China: 2020 update. Cell Mol. Immunol. 18, 792–804 (2021).

    Article  CAS  Google Scholar 

  5. Demaria, O. et al. Harnessing innate immunity in cancer therapy. Nature 574, 45–56 (2019).

    Article  CAS  Google Scholar 

  6. Lv, M. et al. Manganese is critical for antitumor immune responses via cGAS-STING and improves the efficacy of clinical immunotherapy. Cell Res. 30, 966–979 (2020).

    Article  CAS  Google Scholar 

  7. Woo, S. R., Corrales, L. & Gajewski, T. F. Innate immune recognition of cancer. Annu Rev. Immunol. 33, 445–474 (2015).

    Article  CAS  Google Scholar 

  8. Gajewski, T. F., Schreiber, H. & Fu, Y. X. Innate and adaptive immune cells in the tumor microenvironment. Nat. Immunol. 14, 1014–1022 (2013).

    Article  CAS  Google Scholar 

  9. Feng, M. et al. Phagocytosis checkpoints as new targets for cancer immunotherapy. Nat. Rev. Cancer 19, 568–586 (2019).

    Article  CAS  Google Scholar 

  10. Fang, F., Xiao, W. & Tian, Z. NK cell-based immunotherapy for cancer. Semin Immunol. 31, 37–54 (2017).

    Article  CAS  Google Scholar 

  11. Myers, J. A. & Miller, J. S. Exploring the NK cell platform for cancer immunotherapy. Nat. Rev. Clin. Oncol. 18, 85–100 (2021).

    Article  Google Scholar 

  12. Klichinsky, M. et al. Human chimeric antigen receptor macrophages for cancer immunotherapy. Nat. Biotechnol. 38, 947–953 (2020).

    Article  CAS  Google Scholar 

  13. Larkin, B. et al. Cutting edge: activation of STING in T cells induces type I IFN responses and cell death. J. Immunol. 199, 397–402 (2017).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

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

Author information

Authors and Affiliations

  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

Authors
  1. Xiaolei Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hanren Dai
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Hua Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Weidong Han
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Hua Wang or Weidong Han.

Ethics declarations

Competing interests

The authors declare no competing interests.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

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

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41423-021-00679-8

This article is cited by

Search

Advanced search

Quick links