Exogenous IL-33 promotes tumor immunity via macroscopic regulation of ILC2s.
Tumor immune microenvironment
cancer immunity
immunotherapy
interleukin-33
type 2 innate lymphoid cell
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
30 10 2024
30 10 2024
Historique:
received:
09
07
2024
accepted:
24
10
2024
medline:
31
10
2024
pubmed:
31
10
2024
entrez:
31
10
2024
Statut:
epublish
Résumé
Interleukin-33 (IL-33) is a pleiotropic molecule that plays various roles in the body. However, how exogenous IL-33 changes the tumor immune microenvironment remains unclear. Our study revealed that exogenous IL-33 exerts anti-tumor effects and effectively suppresses the progression of subcutaneous melanoma. scRNA-seq analysis revealed that exogenous IL-33 reduced neutrophils accumulation, thereby improving the inhibitory immune environment. Flow cytometry analysis revealed that exogenous IL-33 significantly increased the proportion of eosinophils and group 2 innate lymphoid cells (ILC2s). In addition, we identified genes encoding major histocompatibility complex (MHC) class II molecules in this group of ILC2s, suggesting that ILC2s may play a role in antigen presentation. In Il7r
Identifiants
pubmed: 39478174
doi: 10.1038/s41598-024-77751-6
pii: 10.1038/s41598-024-77751-6
doi:
Substances chimiques
Interleukin-33
0
Il33 protein, mouse
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
26140Subventions
Organisme : Special fund of the basic research support program for outstanding young teachers in Heilongjiang Province
ID : YQJH2023032
Organisme : Special fund of the basic research support program for outstanding young teachers in Heilongjiang Province
ID : YQJH2023032
Organisme : Special fund of the basic research support program for outstanding young teachers in Heilongjiang Province
ID : YQJH2023032
Organisme : Special fund of the basic research support program for outstanding young teachers in Heilongjiang Province
ID : YQJH2023032
Organisme : Special fund of the basic research support program for outstanding young teachers in Heilongjiang Province
ID : YQJH2023032
Organisme : Special fund of the basic research support program for outstanding young teachers in Heilongjiang Province
ID : YQJH2023032
Informations de copyright
© 2024. The Author(s).
Références
Liew, F. Y., Girard, J. P. & Turnquist, H. R. Interleukin-33 in health and disease. Nat. Rev. Immunol. 16(11), 676–689. https://doi.org/10.1038/nri.2016.95 (2016).
doi: 10.1038/nri.2016.95
pubmed: 27640624
Carriere, V. et al. IL-33, the IL-1-like cytokine ligand for ST2 receptor, is a chromatin-associated nuclear factor in vivo. P Natl. Acad. Sci. USA. 104(1), 282–287. https://doi.org/10.1073/pnas.0606854104 (2006).
doi: 10.1073/pnas.0606854104
Dwyer, G. K., D’Cruz, L. M. & Turnquist, H. R. Emerging functions of IL-33 in homeostasis and immunity. Annu. Rev. Immunol. 40, 15–43. https://doi.org/10.1146/annurev-immunol-101320-124243 (2022).
doi: 10.1146/annurev-immunol-101320-124243
pubmed: 34985928
Martin, N. T. & Martin, M. U. Interleukin 33 is a guardian of barriers and a local alarmin. Nat. Immunol. 17(2), 122–131. https://doi.org/10.1038/ni.3370 (2016).
doi: 10.1038/ni.3370
pubmed: 26784265
Palmer, G., Moulin, D., Donzé, O., Talabot-Ayer, D. & Gabay, C. IL-33: a novel cytokine with proinflammatory properties. Arthritis Res. Ther. 9, P9. https://doi.org/10.1186/ar2235 (2007).
doi: 10.1186/ar2235
pmcid: 4061935
Perri, G. et al. Interleukin 33 supports squamous cell carcinoma growth via a dual effect on tumour proliferation, migration and invasion, and T cell activation. Cancer Immunol. Immun. 73(6), 110. https://doi.org/10.1007/s00262-024-03676-8 (2024).
doi: 10.1007/s00262-024-03676-8
He, P. Y. et al. Interleukin-33/serum stimulation-2 pathway: Regulatory mechanisms and emerging implications in immune and inflammatory diseases. Cytokine Growth F R. 76, 112–126. https://doi.org/10.1016/j.cytogfr.2023.12.001 (2023).
doi: 10.1016/j.cytogfr.2023.12.001
Mok, M. Y., Luo, C. Y., Huang, F. P., Kong, W. Y. & Chan, G. C. F. IL-33 orchestrated the interaction and immunoregulatory functions of alternatively activated macrophages and regulatory T cells in vitro. J. Immunol. 211(7), 1134–1143. https://doi.org/10.4049/jimmunol.2300191 (2023).
doi: 10.4049/jimmunol.2300191
pubmed: 37566486
Holgado, A. et al. A20 is a master switch of IL-33 signaling in macrophages and determines IL-33-induced lung immunity. J. Allergy Clin. Immun. 152(1), 244–256. https://doi.org/10.1016/j.jaci.2023.02.026 (2023).
doi: 10.1016/j.jaci.2023.02.026
pubmed: 36898482
Dominguez, D. et al. Exogenous IL-33 restores dendritic cell activation and maturation in established cancer. J. Immunol. 198(3), 1365–1375. https://doi.org/10.4049/jimmunol.1501399 (2016).
doi: 10.4049/jimmunol.1501399
pubmed: 28011934
Wan, J. et al. ILC2-derived IL-9 inhibits colorectal cancer progression by activating CD8 + T cells. Cancer Lett. 502, 34–43. https://doi.org/10.1016/j.canlet.2021.01.002 (2021).
doi: 10.1016/j.canlet.2021.01.002
pubmed: 33429004
Hollande, C. et al. Inhibition of the dipeptidyl peptidase DPP4 (CD26) reveals IL-33-dependent eosinophil-mediated control of tumor growth. Nat. Immunol. 20(3), 257–264. https://doi.org/10.1038/s41590-019-0321-5 (2019).
doi: 10.1038/s41590-019-0321-5
pubmed: 30778250
Jacquelot, N. et al. Blockade of the co-inhibitory molecule PD-1 unleashes ILC2-dependent antitumor immunity in melanoma. Nat. Immunol. 22(7), 851–864. https://doi.org/10.1038/s41590-021-00943-z (2021).
doi: 10.1038/s41590-021-00943-z
pubmed: 34099918
Yeoh, W. J., Vu, V. P. & Krebs, P. IL-33 biology in cancer: An update and future perspectives. Cytokine. 157, 155961. https://doi.org/10.1016/j.cyto.2022.155961 (2022).
doi: 10.1016/j.cyto.2022.155961
pubmed: 35843125
Che, K. et al. Macrophages reprogramming improves immunotherapy of IL-33 in peritoneal metastasis of gastric cancer. Embo Mol. Med. 16(2), 251–266. https://doi.org/10.1038/s44321-023-00012-y (2024).
doi: 10.1038/s44321-023-00012-y
pubmed: 38238529
Saranchova, I. et al. A novel type-2 innate lymphoid cell-based immunotherapy for cancer. Front. Immunol. 15, 1317522. https://doi.org/10.3389/fimmu.2024.1317522 (2024).
doi: 10.3389/fimmu.2024.1317522
pubmed: 38524132
Park, J. H. et al. Nuclear IL-33/SMAD signaling axis promotes cancer development in chronic inflammation. Embo J. 40(7), e106151. https://doi.org/10.15252/embj.2020106151 (2021).
doi: 10.15252/embj.2020106151
pubmed: 33616251
Zhao, M. et al. IL-33/ST2 signaling promotes constitutive and inductive PD-L1 expression and immune escape in oral squamous cell carcinoma. Brit J. Cancer 128(5), 833–843. https://doi.org/10.1038/s41416-022-02090-0 (2022).
doi: 10.1038/s41416-022-02090-0
pubmed: 36463324
Dai, J. Z. et al. Obesity-mediated upregulation of the YAP/IL33 signaling axis promotes aggressiveness and induces an immunosuppressive tumor microenvironment in breast cancer. J. Cell. Physiol. 238(5), 992–1005. https://doi.org/10.1002/jcp.30985 (2023).
doi: 10.1002/jcp.30985
pubmed: 36852589
Faas, M. et al. IL-33-induced metabolic reprogramming controls the differentiation of alternatively activated macrophages and the resolution of inflammation. Immunity. 54(11), 2531–2546. https://doi.org/10.1016/j.immuni.2021.09.010 (2021).
doi: 10.1016/j.immuni.2021.09.010
pubmed: 34644537
Lu, H. F. et al. ILC2s: Unraveling the innate immune orchestrators in allergic inflammation. Int. Immunopharmaccol. 131, 111899. https://doi.org/10.1016/j.intimp.2024.111899 (2024).
doi: 10.1016/j.intimp.2024.111899
Li, Z. et al. Therapeutic application of human type 2 innate lymphoid cells via induction of granzyme B-mediated tumor cell death. Cell. 187(3), 624–641. https://doi.org/10.1016/j.cell.2023.12.015 (2024).
doi: 10.1016/j.cell.2023.12.015
pubmed: 38211590
Howard, E. et al. PD-1 blockade on tumor microenvironment-resident ILC2s promotes TNF-α production and restricts progression of metastatic melanoma. Front. Immunol. 12, 733136. https://doi.org/10.3389/fimmu.2021.733136 (2021).
doi: 10.3389/fimmu.2021.733136
pubmed: 34531874
Yuan, X., Rasul, F., Nashan, B. & Sun, C. Innate lymphoid cells and cancer: Role in tumor progression and inhibition. Eur. J. Immunol. 51(9), 2188–2205. https://doi.org/10.1002/eji.202049033 (2021).
doi: 10.1002/eji.202049033
pubmed: 34189723
Spits, H. & Mjösberg, J. Heterogeneity of type 2 innate lymphoid cells. Nat. Rev. Immunol. 22(11), 701–712. https://doi.org/10.1038/s41577-022-00704-5 (2022).
doi: 10.1038/s41577-022-00704-5
pubmed: 35354980
Trabanelli, S. et al. Tumour-derived PGD2 and NKp30-B7H6 engagement drives an immunosuppressive ILC2-MDSC axis. Nat. Commun. 8(1), 593. https://doi.org/10.1038/s41467-017-00678-2 (2017).
doi: 10.1038/s41467-017-00678-2
pubmed: 28928446
Konjević, G. M., Vuletić, A. M., Mirjačić Martinović, K. M. & Larsen, A. K. & Jurišić, V. B. The role of cytokines in the regulation of NK cells in the tumor environment. Cytokine. 117, 30–40. https://doi.org/10.1016/j.cyto.2019.02.001 (2019).
doi: 10.1016/j.cyto.2019.02.001
pubmed: 30784898
Jou, E. et al. An innate IL-25-ILC2-MDSC axis creates a cancer-permissive microenvironment for Apc mutation-driven intestinal tumorigenesis. Sci. Immunol. 7(72), abn0175. https://doi.org/10.1126/sciimmunol.abn0175 (2022).
doi: 10.1126/sciimmunol.abn0175
Schwartz, C. et al. ILC2s regulate adaptive Th2 cell functions via PD-L1 checkpoint control. J. Exp. Med. 214(9), 2507–2521. https://doi.org/10.1084/jem.20170051 (2017).
doi: 10.1084/jem.20170051
pubmed: 28747424
Jarick, K. J. et al. Non-redundant functions of group 2 innate lymphoid cells. Nature. 611(7937), 794–800. https://doi.org/10.1038/s41586-022-05395-5 (2022).
doi: 10.1038/s41586-022-05395-5
pubmed: 36323785
pmcid: 7614745
Ercolano, G. et al. PPARɣ drives IL-33-dependent ILC2 pro-tumoral functions. Nat. Commun. 12(1), 2538. https://doi.org/10.1038/s41467-021-22764-2 (2021).
doi: 10.1038/s41467-021-22764-2
pubmed: 33953160
Schuijs, M. J. et al. ILC2-driven innate immune checkpoint mechanism antagonizes NK cell antimetastatic function in the lung. Nat. Immunol. 21(9), 998–1009. https://doi.org/10.1038/s41590-020-0745-y (2020).
doi: 10.1038/s41590-020-0745-y
pubmed: 32747815
Qi, J. et al. Single-cell transcriptomic landscape reveals tumor specific innate lymphoid cells associated with colorectal cancer progression. Cell. Rep. Med. 2(8), 100353. https://doi.org/10.1016/j.xcrm.2021.100353 (2021).
doi: 10.1016/j.xcrm.2021.100353
pubmed: 34467243
Vignali, D. A., Collison, L. W. & Workman, C. J. How regulatory T cells work. Nat. Rev. Immunol. 8(7), 523–532. https://doi.org/10.1038/nri2343 (2008).
doi: 10.1038/nri2343
pubmed: 18566595
Wing, K., & Sakaguchi, S. Regulatory T cells exert checks and balances on self tolerance and autoimmunity. Nat. Immunol. 11(1), 7–13. https://doi.org/10.1038/ni.1818 (2009).
doi: 10.1038/ni.1818
pubmed: 20016504
Whiteside, T. L. What are regulatory T cells (Treg) regulating in cancer and why? Semin Cancer Biol. 22(4). https://doi.org/10.1016/j.semcancer.2012.03.004 (2012). 327 – 34.
Deng, Y. et al. CD122-selective IL-2 complexes treat ovarian carcinomas, induce Treg fragility and promote T cell stem cells. J. Immunother Cancer. 8, A729–A731. https://doi.org/10.1136/jitc-2020-sitc2020.0690 (2020).
doi: 10.1136/jitc-2020-sitc2020.0690
Lucca, L. E. & Dominguez-Villar, M. Modulation of regulatory T cell function and stability by co-inhibitory receptors. Nat. Rev. Immunol. 20(11), 680–693. https://doi.org/10.1038/s41577-020-0296-3 (2020).
doi: 10.1038/s41577-020-0296-3
pubmed: 32269380
Moral, J. A. et al. ILC2s amplify PD-1 blockade by activating tissue-specific cancer immunity. Nature. 579(7797), 130–135. https://doi.org/10.1038/s41586-020-2015-4 (2020).
doi: 10.1038/s41586-020-2015-4
pubmed: 32076273
Barata, J. T., Durum, S. K. & Seddon, B. Flip the coin: IL-7 and IL-7R in health and disease. Nat. Immunol. 20(12), 1584–1593. https://doi.org/10.1038/s41590-019-0479-x (2019).
doi: 10.1038/s41590-019-0479-x
pubmed: 31745336
Kaech, S. M. et al. Selective expression of the interleukin 7 receptor identifies effector CD8 T cells that give rise to long-lived memory cells. Nat. Immunol. 4(12), 1191–1198. https://doi.org/10.1038/ni1009 (2003).
doi: 10.1038/ni1009
pubmed: 14625547
Silva, A. et al. IL-7 contributes to the progression of human T-cell acute lymphoblastic leukemias. Cancer Res. 71(14), 4780–4789. https://doi.org/10.1158/0008-5472.CAN-10-3606 (2011).
doi: 10.1158/0008-5472.CAN-10-3606
pubmed: 21593192
Krzystek-Korpacka, M. et al. Elevated systemic interleukin-7 in patients with colorectal cancer and individuals at high risk of cancer: association with lymph node involvement and tumor location in the right colon. Cancer Immunol. Immun. 66(2), 171–179. https://doi.org/10.1007/s00262-016-1933-3 (2016).
doi: 10.1007/s00262-016-1933-3
Seol, M. A. et al. Interleukin-7 contributes to the invasiveness of prostate cancer cells by promoting epithelial-mesenchymal transition. Sci. Rep. 9(1), 6917. https://doi.org/10.1038/s41598-019-43294-4 (2019).
doi: 10.1038/s41598-019-43294-4
pubmed: 31061414
Bennstein, S. B. & Uhrberg, M. Biology and therapeutic potential of human innate lymphoid cells. Febs J. 289(14), 3967–3981. https://doi.org/10.1111/febs.15866 (2021).
doi: 10.1111/febs.15866
pubmed: 33837637
Akimoto, M. et al. Hypoxia induces downregulation of the tumor-suppressive sST2 in colorectal cancer cells via the HIF-nuclear IL-33-GATA3 pathway. Proc. Natl. Acad. Sci. USA. 120(18), e2218033120. https://doi.org/10.1073/pnas.2218033120 (2023).
doi: 10.1073/pnas.2218033120
pubmed: 37094129
Maric, J. et al. Prostaglandin E2 suppresses human group 2 innate lymphoid cell function. J. Allergy Clin. Immun. 141(5), 1761–1773. https://doi.org/10.1016/j.jaci.2017.09.050 (2017).
doi: 10.1016/j.jaci.2017.09.050
pubmed: 29217133
Ercolano, G., Falquet, M., Vanoni, G., Trabanelli, S. & Jandus, C. ILC2s: new actors in tumor immunity. Front. Immunol. 10, 2801. https://doi.org/10.3389/fimmu.2019.02801 (2019).
doi: 10.3389/fimmu.2019.02801
pubmed: 31849977
Ruf, B., Greten, T. F. & Korangy, F. Innate lymphoid cells and innate-like T cells in cancer - at the crossroads of innate and adaptive immunity. Nat. Rev. Cancer. 23(6), 351–371. https://doi.org/10.1038/s41568-023-00562-w (2023).
doi: 10.1038/s41568-023-00562-w
pubmed: 37081117
Blomberg, O. S. et al. IL-5-producing CD4 + T cells and eosinophils cooperate to enhance response to immune checkpoint blockade in breast cancer. Cancer Cell. 41(1), 106–123. https://doi.org/10.1016/j.ccell.2022.11.014 (2022).
doi: 10.1016/j.ccell.2022.11.014
pubmed: 36525971
Turnquist, H. R. et al. IL-33 expands suppressive CD11b + Gr-1(int) and regulatory T cells, including ST2L + Foxp3 + cells, and mediates regulatory T cell-dependent promotion of cardiac allograft survival. J. Immunol. 187(9), 4598–4610. https://doi.org/10.4049/jimmunol.1100519 (2011).
doi: 10.4049/jimmunol.1100519
pubmed: 21949025
Liu, Q. et al. IL-33-mediated IL-13 secretion by ST2 + Tregs controls inflammation after lung injury. Jci Insight. 4(6). https://doi.org/10.1172/jci.insight.123919 (2019).
Halvorsen, E. C. et al. IL-33 increases ST2 + Tregs and promotes metastatic tumour growth in the lungs in an amphiregulin-dependent manner. Oncoimmunology. 8(2), 1527497. https://doi.org/10.1080/2162402X.2018.1527497 (2018).
doi: 10.1080/2162402X.2018.1527497
Džopalić, T. et al. Effects of galectin-1 on immunomodulatory properties of human monocyte-derived dendritic cells. Growth Factors. 38(5–6), 235–246. https://doi.org/10.1080/08977194.2021.1947267 (2021).
doi: 10.1080/08977194.2021.1947267