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TLR7-based cancer immunotherapy decreases intratumoral myeloid-derived suppressor cells and blocks their immunosuppressive function

Spinetti, Thibaud
Spagnuolo, Lorenzo
Secondini, Chiara
Treinies, Marina
Rüegg, Curzio
Hotz, Christian
Published in Oncoimmunology. 2016, vol. 5, no. 11, e1230578
Abstract Myeloid-derived suppressor cells (MDSC) are a heterogeneous population of immature myeloid cells with the capacity to inhibit immunological responses. During cancer progression, MDSC are recruited to the tumor sites and secondary lymphoid organs, leading to the suppression of the antitumor function of NK and T cells. Here, we show that the TLR7/8 agonist resiquimod (R848) has a direct effect on MDSC populations in tumor-bearing mice. Systemic application of R848 led to a rapid reduction in both intratumoral and circulating MDSC. The subpopulation of monocytic MDSC (m-MDSC) was the most affected by R848 treatment with an up to 5-fold decrease in the tumor. We found that TLR7 stimulation in tumor-bearing mice led to a maturation and differentiation of MDSC with upregulation of the surface molecules CD11c, F4/80, MHC-I, and MHC-II. MDSC treated with R848 lost their immunosuppressive function and acquired instead an antigen-presenting phenotype with the capability to induce specific T-cell proliferation. Importantly, we found that MDSC co-injected s.c. with CT26 tumor cells lost their ability to support tumor growth after pretreatment with R848. Our results demonstrate that treatment of tumor-bearing mice with a TLR7/8 agonist acts directly on MDSC to induce their maturation and leads them to acquire a non-suppressive status. Considering the obstacles posed by MDSC for cancer immunotherapy, targeting these cells by a TLR7/8 agonist may improve immune responses against cancer.
Keywords ImmunotherapyMDSCR848TLR7Myeloid-derived suppressor cells
PMID: 27999739
PMCID: PMC5139641
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Article (Published version) (763 Kb) - public document Free access
Research group Immunopharmacologie du cancer
Swiss Cancer League: KLS-2910-02-2012
Swiss National Science Foundation: 31003A_138284
Swiss National Science Foundation: 310030_156372
Swiss National Science Foundation: PDFMP3_137079
Swiss National Science Foundation: 31003A_135738
(ISO format)
SPINETTI, Thibaud et al. TLR7-based cancer immunotherapy decreases intratumoral myeloid-derived suppressor cells and blocks their immunosuppressive function. In: Oncoimmunology, 2016, vol. 5, n° 11, p. e1230578. doi: 10.1080/2162402X.2016.1230578 https://archive-ouverte.unige.ch/unige:163839

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Deposited on : 2022-10-03

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