2. Academic Validation
  3. Mannose receptor (CD206) activation in tumor-associated macrophages enhances adaptive and innate antitumor immune responses

Mannose receptor (CD206) activation in tumor-associated macrophages enhances adaptive and innate antitumor immune responses

  • Sci Transl Med. 2020 Feb 12;12(530):eaax6337. doi: 10.1126/scitranslmed.aax6337.
Jesse M Jaynes 1 2,  Rushikesh Sable 3,  Michael Ronzetti 4,  Wendy Bautista 5,  Zachary Knotts 3,  Abisola Abisoye-Ogunniyan 2 6,  Dandan Li 3,  Raul Calvo 4,  Myagmarjav Dashnyam 4,  Anju Singh 4,  Theresa Guerin 5,  Jason White 2,  Sarangan Ravichandran 7,  Parimal Kumar 8,  Keyur Talsania 9,  Vicky Chen 9,  Anghesom Ghebremedhin 2,  Balasubramanyam Karanam 2,  Ahmad Bin Salam 2,  Ruksana Amin 2,  Taivan Odzorig 3,  Taylor Aiken 6 10,  Victoria Nguyen 3,  Yansong Bian 3,  Jelani C Zarif 11 12,  Amber E de Groot 13 14,  Monika Mehta 8,  Lixin Fan 15,  Xin Hu 4,  Anton Simeonov 4,  Nathan Pate 5,  Mones Abu-Asab 16,  Marc Ferrer 4,  Noel Southall 4,  Chan-Young Ock 17,  Yongmei Zhao 9,  Henry Lopez 18,  Serguei Kozlov 5,  Natalia de Val 19 20,  Clayton C Yates 21,  Bolormaa Baljinnyam 22,  Juan Marugan 22,  Udo Rudloff 23
Affiliations

Affiliations

  • 1 College of Agriculture, Environment and Nutrition Sciences, Integrative Biosciences Program, Tuskegee University, Tuskegee, AL 36088, USA.
  • 2 Department of Biology and Center for Cancer Research, Tuskegee University, Tuskegee, AL 36088, USA.
  • 3 Rare Tumor Initiative, Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA.
  • 4 National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, MD 20850, USA.
  • 5 Center for Advanced Preclinical Research, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research Inc., Frederick, MD 21702, USA.
  • 6 Thoracic and GI Oncology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA.
  • 7 Advanced Biomedical Computing Center, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research Inc., Frederick, MD 21701, USA.
  • 8 Sequencing Facility and Single Cell Analysis Facility, Advanced Technology Research Facility, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research, Inc., Frederick, MD 21701, USA.
  • 9 CCR-SF Bioinformatics Group, Advanced Biomedical and Computational Sciences, Biomedical Informatics and Data Science, Advanced Technology Research Facility, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research, Inc., Frederick, MD 21701, USA.
  • 10 Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, WI 53792, USA.
  • 11 Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
  • 12 Bloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
  • 13 James Buchanan Brady Urological Institute, Johns Hopkins School of Medicine, Baltimore, MD 21287, USA.
  • 14 Department of Pharmacology and Molecular Sciences, Johns Hopkins School of Medicine, Baltimore, MD 21287, USA.
  • 15 Basic Science Program, Frederick National Laboratory for Cancer Research, SAXS Core Facility, Center for Cancer Research of the National Cancer Institute, Frederick, MD 21701, USA.
  • 16 Section of Histopathology, National Eye Institute, Bethesda, MD 20892, USA.
  • 17 Department of Hemato Oncology, Seoul National University Hospital, Seoul 03080, Korea.
  • 18 MuriGenics Inc., Vallejo, CA 94592, USA.
  • 19 Cancer Research Technology Program, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research Inc., Frederick, MD 21701, USA.
  • 20 Center for Molecular Microscopy, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 21701, USA.
  • 21 Department of Biology and Center for Cancer Research, Tuskegee University, Tuskegee, AL 36088, USA. cyates@tuskegee.edu baljinnb@mail.nih.gov maruganj@mail.nih.gov rudloffu@mail.nih.gov.
  • 22 National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, MD 20850, USA. cyates@tuskegee.edu baljinnb@mail.nih.gov maruganj@mail.nih.gov rudloffu@mail.nih.gov.
  • 23 Rare Tumor Initiative, Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA. cyates@tuskegee.edu baljinnb@mail.nih.gov maruganj@mail.nih.gov rudloffu@mail.nih.gov.
PMID: 32051227 DOI: 10.1126/scitranslmed.aax6337
Abstract

Solid tumors elicit a detectable immune response including the infiltration of tumor-associated macrophages (TAMs). Unfortunately, this immune response is co-opted into contributing toward tumor growth instead of preventing its progression. We seek to reestablish an antitumor immune response by selectively targeting surface receptors and endogenous signaling processes of the macrophage subtypes driving Cancer progression. RP-182 is a synthetic 10-mer amphipathic analog of host defense peptides that selectively induces a conformational switch of the Mannose Receptor CD206 expressed on TAMs displaying an M2-like phenotype. RP-182-mediated activation of this receptor in human and murine M2-like macrophages elicits a program of endocytosis, phagosome-lysosome formation, and Autophagy and reprograms M2-like TAMs to an antitumor M1-like phenotype. In syngeneic and autochthonous murine Cancer models, RP-182 suppressed tumor growth, extended survival, and was an effective combination partner with chemo- or immune checkpoint therapy. Antitumor activity of RP-182 was also observed in CD206high patient-derived xenotransplantation models. Mechanistically, via selective reduction of immunosuppressive M2-like TAMs, RP-182 improved adaptive and innate antitumor immune responses, including increased Cancer cell phagocytosis by reprogrammed TAMs.

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