Moderate Low UVB Irradiation Modulates Tumor-associated Macrophages and Dendritic Cells and Promotes Antitumor Immunity in Tumor-bearing Mice

Overview

Journal Photochem Photobiol

Specialties Biochemistry
Biology
Chemistry

Date 2022 Aug 13

PMID 35962531

Authors

Gayoung Park

Yan-Hong Cui

Seungwon Yang

Ming Sun

Emma Wilkinson

Haixia Li

Yuhan Blair Zhang

Jing Chen

Marc Bissonnette

Wenbin Lin

Yu-Ying He

Affiliations

Soon will be listed here.

Abstract

Excessive, high doses of ultraviolet B (UVB) UVB irradiation are known to cause skin cancer, aging and immunosuppression. On the contrary, moderate low doses of UVB irradiation are shown to be essential and beneficial to human health, including a tumor-suppressive effect. However, the mechanism by which low levels of UVB suppress tumorigenesis remains unclear. Here, using tumor-bearing mouse models, we show that moderate low repetitive UVB irradiation increases the percentage of activated CD4 and CD8 T cells, and CD103 conventional type 1 dendritic cells (cDC1s), while it decreases the number of immunosuppressive, M2-like macrophages in the tumors. Finally, in mice, deletion of Batf3, a transcription factor critical for the development of conventional dendritic cells, including the CD103 cDC1s, showed increased tumor growth in both sham- and UVB-irradiated mice. Our findings demonstrate that moderate low UVB irradiation inhibits M2-like tumor-associated macrophages, increases CD103 cDC1s and promotes antitumor immunity in mice with an established tumor.

References

Kim Y, He Y . Ultraviolet radiation-induced non-melanoma skin cancer: Regulation of DNA damage repair and inflammation. Genes Dis. 2015; 1(2):188-198. PMC: 4307792. DOI: 10.1016/j.gendis.2014.08.005. View

Hong S, Kim M, Jung M, Jeon H, Goo J, Ahn S . Biopositive effects of low-dose UVB on epidermis: coordinate upregulation of antimicrobial peptides and permeability barrier reinforcement. J Invest Dermatol. 2008; 128(12):2880-7. DOI: 10.1038/jid.2008.169. View

Moozhipurath R, Kraft L, Skiera B . Evidence of protective role of Ultraviolet-B (UVB) radiation in reducing COVID-19 deaths. Sci Rep. 2020; 10(1):17705. PMC: 7572372. DOI: 10.1038/s41598-020-74825-z. View

Mildner A, Jung S . Development and function of dendritic cell subsets. Immunity. 2014; 40(5):642-56. DOI: 10.1016/j.immuni.2014.04.016. View

Qiang L, Sample A, Shea C, Soltani K, Macleod K, He Y . Autophagy gene ATG7 regulates ultraviolet radiation-induced inflammation and skin tumorigenesis. Autophagy. 2017; 13(12):2086-2103. PMC: 5788558. DOI: 10.1080/15548627.2017.1380757. View

van der Leun A, Thommen D, Schumacher T . CD8 T cell states in human cancer: insights from single-cell analysis. Nat Rev Cancer. 2020; 20(4):218-232. PMC: 7115982. DOI: 10.1038/s41568-019-0235-4. View

Cui Y, Yang S, Wei J, Shea C, Zhong W, Wang F . Autophagy of the mA mRNA demethylase FTO is impaired by low-level arsenic exposure to promote tumorigenesis. Nat Commun. 2021; 12(1):2183. PMC: 8041927. DOI: 10.1038/s41467-021-22469-6. View

Noy R, Pollard J . Tumor-associated macrophages: from mechanisms to therapy. Immunity. 2014; 41(1):49-61. PMC: 4137410. DOI: 10.1016/j.immuni.2014.06.010. View

Steinman R . Decisions about dendritic cells: past, present, and future. Annu Rev Immunol. 2011; 30:1-22. DOI: 10.1146/annurev-immunol-100311-102839. View

10.

Spranger S, Dai D, Horton B, Gajewski T . Tumor-Residing Batf3 Dendritic Cells Are Required for Effector T Cell Trafficking and Adoptive T Cell Therapy. Cancer Cell. 2017; 31(5):711-723.e4. PMC: 5650691. DOI: 10.1016/j.ccell.2017.04.003. View

11.

Wculek S, Cueto F, Mujal A, Melero I, Krummel M, Sancho D . Dendritic cells in cancer immunology and immunotherapy. Nat Rev Immunol. 2019; 20(1):7-24. DOI: 10.1038/s41577-019-0210-z. View

12.

Zhu H, Wang N, Yao L, Chen Q, Zhang R, Qian J . Moderate UV Exposure Enhances Learning and Memory by Promoting a Novel Glutamate Biosynthetic Pathway in the Brain. Cell. 2018; 173(7):1716-1727.e17. DOI: 10.1016/j.cell.2018.04.014. View

13.

Theisen D, Ferris S, Briseno C, Kretzer N, Iwata A, Murphy K . -Dependent Genes Control Tumor Rejection Induced by Dendritic Cells Independently of Cross-Presentation. Cancer Immunol Res. 2018; 7(1):29-39. DOI: 10.1158/2326-6066.CIR-18-0138. View

14.

Sontheimer C, Liggitt D, Elkon K . Ultraviolet B Irradiation Causes Stimulator of Interferon Genes-Dependent Production of Protective Type I Interferon in Mouse Skin by Recruited Inflammatory Monocytes. Arthritis Rheumatol. 2016; 69(4):826-836. PMC: 5659322. DOI: 10.1002/art.39987. View

15.

Edelson B, Kc W, Juang R, Kohyama M, Benoit L, Klekotka P . Peripheral CD103+ dendritic cells form a unified subset developmentally related to CD8alpha+ conventional dendritic cells. J Exp Med. 2010; 207(4):823-36. PMC: 2856032. DOI: 10.1084/jem.20091627. View

16.

Rebel H, Dingemanse-van der Spek C, Salvatori D, van Leeuwen J, Robanus-Maandag E, de Gruijl F . UV exposure inhibits intestinal tumor growth and progression to malignancy in intestine-specific Apc mutant mice kept on low vitamin D diet. Int J Cancer. 2014; 136(2):271-7. DOI: 10.1002/ijc.29002. View

17.

Yang Z, Yang S, Cui Y, Wei J, Shah P, Park G . METTL14 facilitates global genome repair and suppresses skin tumorigenesis. Proc Natl Acad Sci U S A. 2021; 118(35). PMC: 8536359. DOI: 10.1073/pnas.2025948118. View

18.

Merad M, Sathe P, Helft J, Miller J, Mortha A . The dendritic cell lineage: ontogeny and function of dendritic cells and their subsets in the steady state and the inflamed setting. Annu Rev Immunol. 2013; 31:563-604. PMC: 3853342. DOI: 10.1146/annurev-immunol-020711-074950. View

19.

Yang S, Wei J, Cui Y, Park G, Shah P, Deng Y . mA mRNA demethylase FTO regulates melanoma tumorigenicity and response to anti-PD-1 blockade. Nat Commun. 2019; 10(1):2782. PMC: 6592937. DOI: 10.1038/s41467-019-10669-0. View

20.

Barragan M, Good M, Kolls J . Regulation of Dendritic Cell Function by Vitamin D. Nutrients. 2015; 7(9):8127-51. PMC: 4586578. DOI: 10.3390/nu7095383. View