Group 2 Innate Lymphoid Cells Boost CD8 T-cell Activation in Anti-tumor Immune Responses

Overview

Journal Oncoimmunology

Specialty Allergy & Immunology

Date 2023 Aug 14

PMID 37577145

Authors

Jing Wen

Shipeng Cheng

Ran Wang

Yuying Huang

Long Xu

Liyan Ma

Zhiyang Ling

Jinfu Xu

Deping Zhao

Yaguang Zhang

Bing Sun

Affiliations

Soon will be listed here.

Abstract

Group 2 innate lymphoid cells (ILC2s) are essential for orchestrating type 2 immune responses during allergic airway inflammation and infection. ILC2s have been reported to play a regulatory role in tumors; however, this conclusion is controversial. In this study, we showed that IL-33-activated ILC2s could boost CD8 T-cell function through direct antigen cross-presentation. After activation by IL-33, ILC2s showed an enhanced potential to process antigens and prime CD8 T cell activation. Activated ILC2s could phagocytose exogenous antigens and , promoting antigen-specific CD8 T cell function to enhance antitumor immune responses. Administration of OVA-loaded ILC2s induces robust antitumor effects on the OVA-expressing tumor model. These findings suggested that the administration of tumor antigen-loaded ILC2s might serve as a potential strategy for cancer treatment.

Citing Articles

Dynamics of tissue repair regulatory T cells and damage in acute Trypanosoma cruzi infection.

Boccardo S, Rodriguez C, Gimenez C, Araujo Furlan C, Abrate C, Almada L PLoS Pathog. 2025; 21(1):e1012906.

PMID: 39883714 PMC: 11813105. DOI: 10.1371/journal.ppat.1012906.

References

Molofsky A, Van Gool F, Liang H, Van Dyken S, Nussbaum J, Lee J . Interleukin-33 and Interferon-γ Counter-Regulate Group 2 Innate Lymphoid Cell Activation during Immune Perturbation. Immunity. 2015; 43(1):161-74. PMC: 4512852. DOI: 10.1016/j.immuni.2015.05.019. View

Pelly V, Kannan Y, Coomes S, Entwistle L, Ruckerl D, Seddon B . IL-4-producing ILC2s are required for the differentiation of T2 cells following Heligmosomoides polygyrus infection. Mucosal Immunol. 2016; 9(6):1407-1417. PMC: 5257265. DOI: 10.1038/mi.2016.4. View

Ferreira A, Szeto A, Heycock M, Clark P, Walker J, Crisp A . RORα is a critical checkpoint for T cell and ILC2 commitment in the embryonic thymus. Nat Immunol. 2021; 22(2):166-178. PMC: 7116838. DOI: 10.1038/s41590-020-00833-w. View

Grigg J, Shanmugavadivu A, Regen T, Parkhurst C, Ahmed A, Joseph A . Antigen-presenting innate lymphoid cells orchestrate neuroinflammation. Nature. 2021; 600(7890):707-712. PMC: 8702489. DOI: 10.1038/s41586-021-04136-4. View

Moro K, Yamada T, Tanabe M, Takeuchi T, Ikawa T, Kawamoto H . Innate production of T(H)2 cytokines by adipose tissue-associated c-Kit(+)Sca-1(+) lymphoid cells. Nature. 2009; 463(7280):540-4. DOI: 10.1038/nature08636. View

Eberl G, Colonna M, Di Santo J, McKenzie A . Innate lymphoid cells. Innate lymphoid cells: a new paradigm in immunology. Science. 2015; 348(6237):aaa6566. PMC: 5658207. DOI: 10.1126/science.aaa6566. View

Lehmann F, von Burg N, Ivanek R, Teufel C, Horvath E, Peter A . Microbiota-induced tissue signals regulate ILC3-mediated antigen presentation. Nat Commun. 2020; 11(1):1794. PMC: 7156681. DOI: 10.1038/s41467-020-15612-2. View

Noval Rivas M, Burton O, Oettgen H, Chatila T . IL-4 production by group 2 innate lymphoid cells promotes food allergy by blocking regulatory T-cell function. J Allergy Clin Immunol. 2016; 138(3):801-811.e9. PMC: 5014699. DOI: 10.1016/j.jaci.2016.02.030. View

Okuyama Y, Okajima A, Sakamoto N, Hashimoto A, Tanabe R, Kawajiri A . IL-33-ILC2 axis promotes anti-tumor CD8 T cell responses via OX40 signaling. Biochem Biophys Res Commun. 2022; 637:9-16. DOI: 10.1016/j.bbrc.2022.11.006. View

10.

Liu L, Ye T, Han Y, Song H, Zhang Y, Xia Y . Reductions in myeloid-derived suppressor cells and lung metastases using AZD4547 treatment of a metastatic murine breast tumor model. Cell Physiol Biochem. 2014; 33(3):633-45. DOI: 10.1159/000358640. View

11.

Sonnenberg G, Hepworth M . Functional interactions between innate lymphoid cells and adaptive immunity. Nat Rev Immunol. 2019; 19(10):599-613. PMC: 6982279. DOI: 10.1038/s41577-019-0194-8. View

12.

Filley A, Dey M . Dendritic cell based vaccination strategy: an evolving paradigm. J Neurooncol. 2017; 133(2):223-235. PMC: 5532060. DOI: 10.1007/s11060-017-2446-4. View

13.

Anderson C, Brossay L . The role of MHC class Ib-restricted T cells during infection. Immunogenetics. 2016; 68(8):677-91. PMC: 5003733. DOI: 10.1007/s00251-016-0932-z. View

14.

Gurram R, Zhu J . Orchestration between ILC2s and Th2 cells in shaping type 2 immune responses. Cell Mol Immunol. 2019; 16(3):225-235. PMC: 6460501. DOI: 10.1038/s41423-019-0210-8. View

15.

Wan J, Wu Y, Huang L, Tian Y, Ji X, Abdelaziz M . ILC2-derived IL-9 inhibits colorectal cancer progression by activating CD8 T cells. Cancer Lett. 2021; 502:34-43. DOI: 10.1016/j.canlet.2021.01.002. View

16.

Oliphant C, Hwang Y, Walker J, Salimi M, Wong S, Brewer J . MHCII-mediated dialog between group 2 innate lymphoid cells and CD4(+) T cells potentiates type 2 immunity and promotes parasitic helminth expulsion. Immunity. 2014; 41(2):283-95. PMC: 4148706. DOI: 10.1016/j.immuni.2014.06.016. View

17.

Boon T, Cerottini J, Van den Eynde B, van der Bruggen P, Van Pel A . Tumor antigens recognized by T lymphocytes. Annu Rev Immunol. 1994; 12:337-65. DOI: 10.1146/annurev.iy.12.040194.002005. View

18.

Chevalier M, Trabanelli S, Racle J, Salome B, Cesson V, Gharbi D . ILC2-modulated T cell-to-MDSC balance is associated with bladder cancer recurrence. J Clin Invest. 2017; 127(8):2916-2929. PMC: 5531411. DOI: 10.1172/JCI89717. View

19.

Chen L, Flies D . Molecular mechanisms of T cell co-stimulation and co-inhibition. Nat Rev Immunol. 2013; 13(4):227-42. PMC: 3786574. DOI: 10.1038/nri3405. View

20.

Jacquelot N, Seillet C, Wang M, Pizzolla A, Liao Y, Hediyeh-Zadeh S . Blockade of the co-inhibitory molecule PD-1 unleashes ILC2-dependent antitumor immunity in melanoma. Nat Immunol. 2021; 22(7):851-864. PMC: 7611091. DOI: 10.1038/s41590-021-00943-z. View