Senescent cancer cells, which are characteristically present in tumors after genotoxic therapies, upregulate the immune checkpoint ligand programmed cell death 1 ligand 2 (PD-L2). We show that genetic or pharmacological ablation of PD-L2 prevents the accumulation of intratumoral senescent cells, reducing the recruitment of immunosuppressive myeloid cells and facilitating tumor clearance by T cells.
This is a preview of subscription content, access via your institution
Access options
Access Nature and 54 other Nature Portfolio journals
Get Nature+, our best-value online-access subscription
$29.99 / 30 days
cancel any time
Subscribe to this journal
Receive 12 digital issues and online access to articles
$119.00 per year
only $9.92 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
References
Toso, A. et al. Enhancing chemotherapy efficacy in Pten-deficient prostate tumors by activating the senescence-associated antitumor immunity. Cell Rep. 9, 75–89 (2014). This paper mechanistically links senescence and immunosuppression in cancer.
Eggert, T. et al. Distinct functions of senescence-associated immune responses in liver tumor surveillance and tumor progression. Cancer Cell 30, 533–547 (2016). This paper explores the context-dependent role of senescence in relation to immunosuppression.
Ruhland, M. K. et al. Stromal senescence establishes an immunosuppressive microenvironment that drives tumorigenesis. Nat. Commun. 7, 11762 (2016). This paper presents evidence of immunosuppression driven by age-related senescence.
Prieto, L. I. et al. Senescent cells as thermostats of antitumor immunity. Sci. Transl. Med. 15, eadg7291 (2023). A review article that summarizes the interaction between senescent and immune cells in cancer.
Shahbandi, A. et al. Breast cancer cells survive chemotherapy by activating targetable immune-modulatory programs characterized by PD-L1 and CD80. Nat. Cancer 3, 1513–1533 (2022). This paper reports the anti-tumoral activity of immunotherapy against therapy-induced senescence in mice.
Additional information
Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
This is a summary of: Chaib, S. et al. The efficacy of chemotherapy is limited by intratumoral senescent cells expressing PD-L2. Nat. Cancer https://doi.org/10.1038/s43018-023-00712-x (2024).
Rights and permissions
About this article
Cite this article
PD-L2 expression in senescent cancer cells limits tumor clearance after chemotherapy. Nat Cancer 5, 382–383 (2024). https://doi.org/10.1038/s43018-023-00713-w
Published:
Issue Date:
DOI: https://doi.org/10.1038/s43018-023-00713-w
