Skip to content
DraconiticResearch
Search Sources API
203,234 studies31 sourcesUpdated 24 min ago
Peer-reviewedCC BY-NC 4.0PNAS Nexus

PPP2R1A-mediated tumor-stromal adhesion as an unrecognized mechanism of immunosuppression

  • Christopher Markosian1,2
  • Daniela I Staquicini1,2
  • Fenny H F Tang1,2
  • Dawn R Christianson3
  • Tracey L Smith1,2
  • Wadih Arap1,4
  • Renata Pasqualini1,2
4 affiliations
  1. 1Rutgers Cancer Institute , Newark, NJ ,
  2. 2Division of Cancer Biology, Department of Radiation Oncology, Rutgers New Jersey Medical School , Newark, NJ ,
  3. 3Christianson Consulting , San Diego, CA ,
  4. 4Division of Hematology/Oncology, Department of Medicine, Rutgers New Jersey Medical School , Newark, NJ ,
Read full textPDFDOICite

Abstract

PPP2R1A, the predominant scaffolding subunit of the larger serine/threonine protein phosphatase 2A (PP2A), has been implicated in several solid tumors. Recently, somatic inactivating mutations in PPP2R1A have been shown to be associated with increased intratumoral inflammation and improved survival in patients undergoing dual immune checkpoint blockade for platinum-resistant ovarian clear-cell carcinoma. However, the structural and functional basis for this biological phenomenon has not yet been elucidated. We have previously reported PPP2R1A-mediated heterotypic-homodimeric protein-protein interactions between melanoma cells and lymphatic endothelial cells. Here, we demonstrate that PPP2R1A is also present on the surface of ovarian cancer cells. Moreover, we propose that the disruption of such tumor-lymphatic homodimeric interactions and thereby their interface may potentially be a causative factor for enhanced immune cell enrichment and inflammatory signaling within the tumor microenvironment, ultimately translating to improved survival with immune checkpoint inhibitors.

Related

  1. 241 Engineering CAR-T cell resistance to CAF-derived paracrine cAMP-mediated immunosuppression
    Gheath Alatrash, Ranjan Upadhyay, Vakul Mohanty +14
    Journal for ImmunoTherapy of CancerPeer-reviewedCC BYFull textOncologyDOAJ
  2. Fatty acids in the tumor microenvironment reprogram neutrophils to induce adenosine-mediated immunosuppression in mice
    Rashi Singhal, Nina W. Zhang, Zheng Hong Lee +26
    Nature CommunicationsPeer-reviewedCC BY-NC-ND 4.0Full textPhysiologyCrossref
  3. MAGI3 Acts as an Intestinal Epithelial Gatekeeper in Inflammation‐Associated Colorectal Cancer by Suppressing the STAT3‐CCL2 Axis and TAM‐Mediated Immunosuppression
    Yumeng Yang, Zhigang Bai, Haibo Wang +10
    Advanced SciencePeer-reviewedCC BY 4.0Full textOncologyPMC
  4. GITRL COEXPRESSION IN ANTI-GD2 CAR-T CELLS ENHANCES RESISTANCE TO TREG-MEDIATED IMMUNOSUPPRESSION, MITIGATES EXHAUSTION, AND BOOSTS CYTOTOXICITY AGAINST GLIOBLASTOMA SPHEROIDS AND ORGANOTYPIC TUMOR SLICES
    Izadora Peter FURTADO, Millena BRANDãO, Raíssa Raminelli REZENDE +5
    Hematology, Transfusion and Cell TherapyPeer-reviewedCC BYFull textOncologyDOAJ
  5. Investigating the Expression and Function of PPP2R1A in Hepatocellular Carcinoma: A Multi-Omics Analysis with in vitro Validation.
    Jinna Tan, Yangling Zeng, Hemeng Wu +10
    Journal of hepatocellular carcinomaPeer-reviewedCC BY-NCFull textGeneral medicineEurope PMC

Cite

BibTeXRIS
BibTeX
@article{markosian2026ppp2r1amediated,
  title = {{PPP2R1A-mediated tumor-stromal adhesion as an unrecognized mechanism of immunosuppression}},
  author = {Christopher Markosian and Daniela I Staquicini and Fenny H F Tang and Dawn R Christianson and Tracey L Smith and Wadih Arap and Renata Pasqualini},
  journal = {PNAS Nexus},
  year = {2026},
  month = oct,
  doi = {10.1093/pnasnexus/pgag362},
  url = {https://academic.oup.com/pnasnexus/advance-article/doi/10.1093/pnasnexus/pgag362/8979533},
  note = {CC BY-NC 4.0},
}
RIS
TY  - JOUR
TI  - PPP2R1A-mediated tumor-stromal adhesion as an unrecognized mechanism of immunosuppression
AU  - Christopher Markosian
AU  - Daniela I Staquicini
AU  - Fenny H F Tang
AU  - Dawn R Christianson
AU  - Tracey L Smith
AU  - Wadih Arap
AU  - Renata Pasqualini
PY  - 2026
DA  - 2026/10/22
JO  - PNAS Nexus
DO  - 10.1093/pnasnexus/pgag362
UR  - https://academic.oup.com/pnasnexus/advance-article/doi/10.1093/pnasnexus/pgag362/8979533
AB  - PPP2R1A, the predominant scaffolding subunit of the larger serine/threonine protein phosphatase 2A (PP2A), has been implicated in several solid tumors. Recently, somatic inactivating mutations in PPP2R1A have been shown to be associated with increased intratumoral inflammation and improved survival in patients undergoing dual immune checkpoint blockade for platinum-resistant ovarian clear-cell carcinoma. However, the structural and functional basis for this biological phenomenon has not yet been elucidated. We have previously reported PPP2R1A-mediated heterotypic-homodimeric protein-protein interactions between melanoma cells and lymphatic endothelial cells. Here, we demonstrate that PPP2R1A is also present on the surface of ovarian cancer cells. Moreover, we propose that the disruption of such tumor-lymphatic homodimeric interactions and thereby their interface may potentially be a causative factor for enhanced immune cell enrichment and inflammatory signaling within the tumor microenvironment, ultimately translating to improved survival with immune checkpoint inhibitors.
SN  - 2752-6542
ER  -