TLR induced IL-27 plays host-protective role against B16BL6 melanoma in C57BL/6 mice.

Cytokine 2022 Jun

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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. Copyright © 2022 Elsevier Ltd. All rights reserved.

Citation

Ashok Patidar, Sathishkumar Selvaraj, Mohona Chakravarti, Ipsita Guha, Avishek Bhuniya, Saurav Bera, Sukanya Dhar, Kamalika Roy, Rathindranath Baral, Debprasad Chattopadhyay, Chiranjib Pal, Bhaskar Saha. TLR induced IL-27 plays host-protective role against B16BL6 melanoma in C57BL/6 mice. Cytokine. 2022 Jun;154:155871