Decitabine co-operates with the IL-33/ST2 axis modifying the tumor microenvironment and improving the response to PD-1 blockade in melanoma

Afferni C, Buccione C, Andreone S, Galdiero MR, Varricchi G, Marone G, et al. The pleiotropic immunomodulatory functions of IL-33 and its implications in tumor immunity. Front Immunol. 2018;9:2601. https://doi.org/10.3389/fimmu.2018.02601.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Andreone S, Gambardella AR, Mancini J, Loffredo S, Marcella S, La Sorsa V, et al. Anti-tumorigenic activities of IL-33: a mechanistic insight. Front Immunol. 2020;11:571593. https://doi.org/10.3389/fimmu.2020.571593.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Andreone S, Spadaro F, Buccione C, Mancini J, Tinari A, Sestili P, et al. IL-33 promotes CD11b/CD18-mediated adhesion of eosinophils to cancer cells and synapse-polarized degranulation leading to tumor cell killing. Cancers (Basel). 2019;11(11). https://doi.org/10.3390/cancers11111664.

Lucarini V, Ziccheddu G, Macchia I, La Sorsa V, Peschiaroli F, Buccione C, et al. IL-33 restricts tumor growth and inhibits pulmonary metastasis in melanoma-bearing mice through eosinophils. OncoImmunology. 2017;6(6). https://doi.org/10.1080/2162402X.2017.1317420.

Dominguez D, Ye C, Geng Z, Chen S, Fan J, Qin L, et al. Exogenous IL-33 restores dendritic cell activation and maturation in established cancer. J Immunol. 2017;198(3):1365–75. https://doi.org/10.4049/jimmunol.1501399.

Article  CAS  PubMed  Google Scholar 

Gao X, Wang X, Yang Q, Zhao X, Wen W, Li G, et al. Tumoral expression of IL-33 inhibits tumor growth and modifies the tumor microenvironment through CD8+ T and NK cells. J Immunol. 2015;194(1):438–45. https://doi.org/10.4049/jimmunol.1401344.

Article  CAS  PubMed  Google Scholar 

Kim J, Kim W, Moon UJ, Kim HJ, Choi HJ, Sin JI, et al. Intratumorally establishing type 2 innate lymphoid cells blocks tumor growth. J Immunol. 2016;196(5):2410–23. https://doi.org/10.4049/jimmunol.1501730.

Article  CAS  PubMed  Google Scholar 

Yeoh WJ, Vu VP, Krebs P. IL-33 biology in cancer: an update and future perspectives. Cytokine. 2022;157:155961. https://doi.org/10.1016/j.cyto.2022.155961.

Article  CAS  PubMed  Google Scholar 

Chen L, Sun R, Xu J, Zhai W, Zhang D, Yang M, et al. Tumor-derived IL33 promotes tissue-resident CD8+ T cells and is required for checkpoint blockade tumor immunotherapy. Cancer Immunol Res. 2020;8(11):1381–92. https://doi.org/10.1158/2326-6066.CIR-19-1024.

Article  PubMed  PubMed Central  Google Scholar 

Dixit A, Sarver A, Zettervall J, Huang H, Zheng K, Brekken RA, et al. Targeting TNF-α-producing macrophages activates antitumor immunity in pancreatic cancer via IL-33 signaling. JCI Insight. 2022;7(22). https://doi.org/10.1172/jci.insight.153242.

Blomberg OS, Spagnuolo L, Garner H, Voorwerk L, Isaeva OI, van Dyk E, et al. IL-5-producing CD4+ T cells and eosinophils cooperate to enhance response to immune checkpoint blockade in breast cancer. Cancer Cell. 2023;41(1):106–23.e10. https://doi.org/10.1016/j.ccell.2022.11.014.

Article  CAS  PubMed  Google Scholar 

Hollande C, Boussier J, Ziai J, Nozawa T, Bondet V, Phung W, et al. Inhibition of the dipeptidyl peptidase DPP4 (CD26) reveals IL-33-dependent eosinophil-mediated control of tumor growth. Nat Immunol. 2019;20(3):257–64. https://doi.org/10.1038/s41590-019-0321-5.

Article  CAS  PubMed  Google Scholar 

Jacquelot N, Seillet C, Wang M, Pizzolla A, Liao Y, Hediyeh-Zadeh S, et al. Blockade of the co-inhibitory molecule PD-1 unleashes ILC2-dependent antitumor immunity in melanoma. Nat Immunol. 2021;22(7):851–64. https://doi.org/10.1038/s41590-021-00943-z.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Moral JA, Leung J, Rojas LA, Ruan J, Zhao J, Sethna Z, et al. ILC2s amplify PD-1 blockade by activating tissue-specific cancer immunity. Nature. 2020. https://doi.org/10.1038/s41586-020-2015-4.

Article  PubMed  PubMed Central  Google Scholar 

Giunta EF, Arrichiello G, Curvietto M, Pappalardo A, Bosso D, Rosanova M, et al. Epigenetic regulation in melanoma: facts and hopes. Cells. 2021;10(8). https://doi.org/10.3390/cells10082048.

Gracia-Hernandez M, Munoz Z, Villagra A. Enhancing therapeutic approaches for melanoma patients targeting epigenetic modifiers. Cancers (Basel). 2021;13(24). https://doi.org/10.3390/cancers13246180.

Fazio C, Covre A, Cutaia O, Lofiego MF, Tunici P, Chiarucci C, et al. Immunomodulatory properties of DNA hypomethylating agents: selecting the optimal epigenetic partner for cancer immunotherapy. Front Pharmacol. 2018;9:1443. https://doi.org/10.3389/fphar.2018.01443.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Han J, Xu X, Liu Z, Li Z, Wu Y, Zuo D. Recent advances of molecular mechanisms of regulating PD-L1 expression in melanoma. Int Immunopharmacol. 2020;88:106971. https://doi.org/10.1016/j.intimp.2020.106971.

Article  CAS  PubMed  Google Scholar 

Amaro A, Reggiani F, Fenoglio D, Gangemi R, Tosi A, Parodi A, et al. Guadecitabine increases response to combined anti-CTLA-4 and anti-PD-1 treatment in mouse melanoma in vivo by controlling T-cells, myeloid derived suppressor and NK cells. J Exp Clin Cancer Res. 2023;42(1):67. https://doi.org/10.1186/s13046-023-02628-x.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Lucarini V, Buccione C, Ziccheddu G, Peschiaroli F, Sestili P, Puglisi R, et al. Combining type I interferons and 5-Aza-2?-deoxycitidine to improve anti-tumor response against melanoma. J Investig Dermatol. 2017;137(1):159–69. https://doi.org/10.1016/j.jid.2016.08.024.

Article  CAS  PubMed  Google Scholar 

Saleh MH, Wang L, Goldberg MS. Improving cancer immunotherapy with DNA methyltransferase inhibitors. Cancer Immunol Immunother. 2016;65(7):787–96. https://doi.org/10.1007/s00262-015-1776-3.

Article  CAS  PubMed  Google Scholar 

Kozar K, Kamiński R, Switaj T, Ołdak T, Machaj E, Wysocki PJ, et al. Interleukin 12-based immunotherapy improves the antitumor effectiveness of a low-dose 5-Aza-2’-deoxycitidine treatment in L1210 leukemia and B16F10 melanoma models in mice. Clin Cancer Res. 2003;9(8):3124–33.

CAS  PubMed  Google Scholar 

Zhang P, Tao C, Lu Y, Li P, Wang X, Dai Y, et al. Epigenetic reprogramming potentiates ICAM1 antibody drug conjugates in preclinical models of melanoma. Adv Sci (Weinh). 2024;11(30). https://doi.org/10.1002/advs.202400203.

Gordy JT, Sandhu AK, Fessler K, Luo K, Kapoor AR, Ayeh SK, et al. IFNα and 5-Aza-2’-deoxycytidine combined with a dendritic-cell targeting DNA vaccine alter tumor immune cell infiltration in the B16F10 melanoma model. Front Immunol. 2022;13:1074644. https://doi.org/10.3389/fimmu.2022.1074644.

Article  CAS  PubMed  Google Scholar 

Gordy JT, Luo K, Kapoor A, Kim ES, Ayeh SK, Karakousis PC, et al. Treatment with an immature dendritic cell-targeting vaccine supplemented with IFN-α and an inhibitor of DNA methylation markedly enhances survival in a murine melanoma model. Cancer Immunol Immunother. 2020;69(4):569–80. https://doi.org/10.1007/s00262-019-02471-0.

Article  CAS  PubMed  PubMed Central  Google Scholar 

De Ninno A, Bertani FR, Gerardino A, Schiavoni G, Musella M, Galassi C, et al. Microfluidic co-culture models for dissecting the immune response in in vitro tumor microenvironments. J Vis Exp. 2021(170). https://doi.org/10.3791/61895.

Verma V, Shrimali RK, Ahmad S, Dai W, Wang H, Lu S, et al. PD-1 blockade in subprimed CD8 cells induces dysfunctional PD-1. Nat Immunol. 2019;20(9):1231–43. https://doi.org/10.1038/s41590-019-0441-y.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Mencattini A, De Ninno A, Mancini J, Businaro L, Martinelli E, Schiavoni G, et al. High-throughput analysis of cell-cell crosstalk in ad hoc designed microfluidic chips for oncoimmunology applications. Methods Enzymol. 2020;632:479–502. https://doi.org/10.1016/bs.mie.2019.06.012.

Article  CAS  PubMed  Google Scholar 

Mattei F, Andreone S, Mencattini A, De Ninno A, Businaro L, Martinelli E, et al. Oncoimmunology meets organs-on-chip. Front Mol Biosci. 2021;8:627454. https://doi.org/10.3389/fmolb.2021.627454.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Attrill GH, Ferguson PM, Palendira U, Long GV, Wilmott JS, Scolyer RA. The tumour immune landscape and its implications in cutaneous melanoma. Pigment Cell Melanoma Res. 2021;34(3):529–49. https://doi.org/10.1111/pcmr.12926.

Article  CAS  PubMed  Google Scholar 

Knight A, Karapetyan L, Kirkwood JM. Immunotherapy in melanoma: recent advances and future directions. Cancers (Basel). 2023;15(4). https://doi.org/10.3390/cancers15041106.

Simiczyjew A, Dratkiewicz E, Mazurkiewicz J, Ziętek M, Matkowski R, Nowak D. The influence of tumor microenvironment on immune escape of melanoma. Int J Mol Sci. 2020;21(21). https://doi.org/10.3390/ijms21218359.

Gao K, Li X, Zhang L, Bai L, Dong W, Shi G, et al. Transgenic expression of IL-33 activates CD8(+) T cells and NK cells and inhibits tumor growth and metastasis in mice. Cancer Lett. 2013;335(2):463–71. https://doi.org/10.1016/j.canlet.2013.03.002.

Article  CAS 

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