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Non-conventional Inhibitory CD4+Foxp3−PD-1hi T Cells as a Biomarker of Immune Checkpoint Blockade Activity
| Content Provider | Scilit |
|---|---|
| Author | Zappasodi, Roberta Budhu, Sadna Hellmann, Matthew D. Postow, Michael A. Senbabaoglu, Yasin Manne, Sasikanth Gasmi, Billel Liu, Cailian Zhong, Hong Li, Yanyun Huang, Alexander C. Hirschhorn-Cymerman, Daniel Panageas, Katherine S. Wherry, E. John Merghoub, Taha Wolchok, Jedd D. |
| Copyright Year | 2018 |
| Description | Journal: Cancer Cell Summary A significant proportion of cancer patients do not respond to immune checkpoint blockade. To better understand the molecular mechanisms underlying these treatments, we explored the role of $CD4^{+}Foxp3^{−}$ T cells expressing PD-1 $(4PD1^{hi}$) and observed that $4PD1^{hi}$ accumulate intratumorally as a function of tumor burden. Interestingly, CTLA-4 blockade promotes intratumoral and peripheral $4PD1^{hi}$ increases in a dose-dependent manner, while combination with PD-1 blockade mitigates this effect and improves anti-tumor activity. We found that lack of effective $4PD1^{hi}$ reduction after anti-PD-1 correlates with poor prognosis. Mechanistically, we provide evidence that mouse and human circulating and intra-tumor $4PD1^{hi}$ inhibit T cell functions in a PD-1/PD-L1 dependent fashion and resemble follicular helper T cell $(T_{FH}$)-like cells. Accordingly, anti-CTLA-4 activity is improved in $T_{FH}$ deficient mice. |
| Related Links | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6648657/pdf http://www.cell.com/article/S153561081830223X/pdf |
| ISSN | 15356108 |
| e-ISSN | 18783686 |
| DOI | 10.1016/j.ccell.2018.05.009 |
| Journal | Cancer Cell |
| Issue Number | 6 |
| Volume Number | 33 |
| Language | English |
| Publisher | Elsevier BV |
| Publisher Date | 2018-06-01 |
| Access Restriction | Open |
| Subject Keyword | Journal: Cancer Cell Cell Biology Cancer Immunotherapy; Immune Checkpoint Blockade; Pd-1; Ctla-4; Pd-l1; Immune Tolerance; Immune Resistance; Cd4+ T Cells; Regulatory T Cells; Follicular Helper T Cells |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Cancer Research Oncology |
