Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Editorial
. 2023 Apr 3;29(7):1167-1169.
doi: 10.1158/1078-0432.CCR-22-3652.

Myeloid Maturity: ATRA to Enhance Anti-PD-1?

Daniel J Olson  1 , Jason J Luke  2
Affiliations
Editorial

Myeloid Maturity: ATRA to Enhance Anti-PD-1?

Daniel J Olson et al. Clin Cancer Res. .

Abstract

Myeloid-derived suppressor cells (MDSC) are associated with resistance to anti-PD-1 therapies. All-trans retinoic acid (ATRA) may induce maturation of MDSCs and alter their immunosuppressive effects. Adding ATRA to pembrolizumab may target this resistance mechanism to enhance the overall impact of anti-PD-1-based immunotherapy. See related article by Tobin et al., p. 1209.

PubMed Disclaimer

Figures

Figure 1:
Figure 1:
MDSCs are associated with primary resistance to anti-PD-1 therapy. The promise of ATRA is to enhance activity of anti-PD-1 therapy through alteration in the maturation state of MDSCs. Relatively immature and immune suppressive MDSCs can be induced by ATRA along the myeloid lineage towards differentiated mature myeloid phenotypes such as monocytes, dendritic cells and neutrophils. This change in turn decreases the immunosuppressive effects of MDSCs and may shift the tumor microenvironment towards a T-cell inflamed tumor phenotype where anti-PD-1 therapy can provide effective antitumor immunity. (Figure created with BioRender.com.)
See this image and copyright information in PMC

Comment in

Comment on

References

    1. Tobin RP, Cogswell DT, Cates VM, Davis DM, Borgers JSW, Van Gulick RJ, et al. Targeting MDSC differentiation using ATRA: a phase I/II clinical trial combining pembrolizumab and all-trans retinoic acid for metastatic melanoma. Clin Cancer Res [Internet]. 2022; Available from: 10.1158/1078-0432.CCR-22-2495 - DOI - PMC - PubMed
    1. Robert C, Ribas A, Schachter J, Arance A, Grob J-J, Mortier L, et al. Pembrolizumab versus ipilimumab in advanced melanoma (KEYNOTE-006): post-hoc 5-year results from an open-label, multicentre, randomised, controlled, phase 3 study. Lancet Oncol. 2019;20:1239–51. - PubMed
    1. Tawbi HA, Schadendorf D, Lipson EJ, Ascierto PA, Matamala L, Castillo Gutiérrez E, et al. Relatlimab and Nivolumab versus Nivolumab in Untreated Advanced Melanoma. N Engl J Med. 2022;386:24–34. - PMC - PubMed
    1. Wolchok JD, Chiarion-Sileni V, Gonzalez R, Grob J-J, Rutkowski P, Lao CD, et al. CheckMate 067: 6.5-year outcomes in patients (pts) with advanced melanoma. J Clin Orthod. Wolters Kluwer; 2021;39:9506–9506.
    1. Li K, Shi H, Zhang B, Ou X, Ma Q, Chen Y, et al. Myeloid-derived suppressor cells as immunosuppressive regulators and therapeutic targets in cancer. Signal Transduct Target Ther. 2021;6:362. - PMC - PubMed

MeSH terms

LinkOut - more resources