Controversial role of the immune checkpoint OX40L expression on platelets in breast cancer progression Journal Article

   


Authors: Rittig, S. M.; Lutz, M. S.; Clar, K. L.; Zhou, Y.; Kropp, K. N.; Koch, A.; Hartkopf, A. D.; Hinterleitner, M.; Zender, L.; Salih, H. R.; Maurer, S.; Hinterleitner, C.
Article Title: Controversial role of the immune checkpoint OX40L expression on platelets in breast cancer progression
Abstract: In conventional T cells, OX40 has been identified as a major costimulating receptor augmenting survival and clonal expansion of effector and memory T cell populations. In regulatory T cells, (Treg) OX40 signaling suppresses cellular activity and differentiation. However, clinical trials investigating OX40 agonists to enhance anti-tumor immunity, showed only limited success so far. Here we show that platelets from breast cancer patients express relevant levels of OX40L and platelet OX40L (pOX40L) inversely correlates with platelet-expressed immune checkpoint molecules GITRL (pGITRL) and TACI (pTACI). While high expression of pOX40L correlates with T and NK cell activation, elevated pOX40L levels identify patients with higher tumor grades, the occurrence of metastases, and shorter recurrence-free survival (RFS). Of note, OX40 mRNA levels in breast cancer correlate with enhanced expression of anti-apoptotic, immune-suppressive, and tumor-promoting mRNA gene signatures. Our data suggest that OX40L on platelets might play counteracting roles in cancer and anti-tumor immunity. Since pOX40L reflects disease relapse better than the routinely used predictive markers CA15-3, CEA, and LDH, it could serve as a novel biomarker for refractory disease in breast cancer. Copyright © 2022 Rittig, Lutz, Clar, Zhou, Kropp, Koch, Hartkopf, Hinterleitner, Zender, Salih, Maurer and Hinterleitner.
Keywords: breast cancer; immunotherapy; biomarker; platelets; prognosis; ox40l
Journal Title: Frontiers in Oncology
Volume: 12
ISSN: 2234-943X
Publisher: Frontiers Media S.A.  
Date Published: 2022-07-01
Start Page: 917834
Language: English
DOI: 10.3389/fonc.2022.917834
PROVIDER: scopus
PMCID: PMC9304936
PUBMED: 35875148
DOI/URL:

https://www.scopus.com/inward/record.uri?eid=2-s2.0-85134650683&doi=10.3389%2ffonc.2022.917834&partnerID=40&md5=25c947f1535ddf525b0b765ede432d91
Notes: Article -- Export Date: 1 August 2022 -- Source: Scopus
Altmetric
What is Altmetric?
Citation Impact
What is Dimensions Citation Badge?
BMJ Impact Analytics
MSK Authors
  1. Clemens Hinterleitner
    8 Hinterleitner
Related MSK Work