TLR induced IL-27 plays host-protective role against B16BL6 melanoma in C57BL/6 mice.
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| Abstract |
Elicitation of the tumor-eliminating immune response is a major challenge, as macrophages- constituting a major component of solid tumor mass- play important roles in development, maintenance and tumor regression. The macrophage-expressed Toll-Like Receptors (TLRs) enhance macrophage function and their ability to activate T cells via secretion of cytokines, which may help in tumor regression. IL-27, a member of the IL-12 family of cytokines, is shown to exhibit anti-tumor and anti-angiogenic activities. Herein, we developed B16BL6 melanoma model in C75BL/6 mouse to dissect the crosstalk between TLRs and IL-27 in tumors. We report existence of a novel TLR- IL-27 feed-forward loop, whereby TLRs and IL-27 up-regulated each other's expression, which we found perturbed during melanoma tumorigenesis. Intra-tumoral injection of Imiquimod, a TLR7/8 ligand, reduced the tumor burden; the anti-tumor effect was reversed upon IL-27 and IL-27R silencing by intra-tumorally administered, lentivirally expressed IL-27 and IL-27R shRNA. The reduced tumor growth was accompanied by significantly fewer Treg cells but increased IFN-γ and granzyme B expression by CD8+ T cells. These data indicate the preventative role for TLR-induced IL-27 in aggressive and highly invasive melanoma.
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| Authors | Ashok Patidar, Sathishkumar Selvaraj, Mohona Chakravarti, Ipsita Guha, Avishek Bhuniya, Saurav Bera, Sukanya Dhar, Kamalika Roy, Rathindranath Baral, Debprasad Chattopadhyay, Chiranjib Pal, Bhaskar Saha |
| Journal | Cytokine (Cytokine) Vol. 154 Pg. 155871 (06 2022) ISSN: 1096-0023 [Electronic] England |
| PMID | 35436657 (Publication Type: Journal Article) |
| Copyright | Copyright © 2022 Elsevier Ltd. All rights reserved. |
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