LAG-3 expression on peripheral blood cells identifies patients with poorer outcomes after immune checkpoint blockade Journal Article
| Authors: | Shen, R.; Postow, M. A.; Adamow, M.; Arora, A.; Hannum, M.; Maher, C.; Wong, P.; Curran, M. A.; Hollmann, T. J.; Jia, L.; Al-Ahmadie, H.; Keegan, N.; Funt, S. A.; Iyer, G.; Rosenberg, J. E.; Bajorin, D. F.; Chapman, P. B.; Shoushtari, A. N.; Betof, A. S.; Momtaz, P.; Merghoub, T.; Wolchok, J. D.; Panageas, K. S.; Callahan, M. K. |
| Article Title: | LAG-3 expression on peripheral blood cells identifies patients with poorer outcomes after immune checkpoint blockade |
| Abstract: | Immune checkpoint blocking antibodies are a cornerstone in cancer treatment; however, they benefit only a subset of patients and biomarkers to guide immune checkpoint blockade (ICB) treatment choices are lacking. We designed this study to identify blood-based correlates of clinical outcome in ICB-treated patients. We performed immune profiling of 188 ICB-treated patients with melanoma using multiparametric flow cytometry to characterize immune cells in pretreatment peripheral blood. A supervised statistical learning approach was applied to a discovery cohort to classify phenotypes and determine their association with survival and treatment response. We identified three distinct immune phenotypes (immunotypes), defined in part by the presence of a LAG-3+CD8+ T cell population. Patients with melanoma with a LAG+ immunotype had poorer outcomes after ICB with a median survival of 22.2 months compared to 75.8 months for those with the LAG− immunotype (P = 0.031). An independent cohort of 94 ICB-treated patients with urothelial carcinoma was used for validation where LAG+ immunotype was significantly associated with response (P = 0.007), survival (P < 0.001), and progression-free survival (P = 0.004). Multivariate Cox regression and stratified analyses further showed that the LAG+ immunotype was an independent marker of outcome when compared to known clinical prognostic markers and previously described markers for the clinical activity of ICB, PD-L1, and tumor mutation burden. The pretreatment peripheral blood LAG+ immunotype detects patients who are less likely to benefit from ICB and suggests a strategy for identifying actionable immune targets for further investigation. © 2021 The Authors, some rights reserved; |
| Journal Title: | Science Translational Medicine |
| Volume: | 13 |
| Issue: | 608 |
| ISSN: | 1946-6234 |
| Publisher: | American Association for the Advancement of Science |
| Date Published: | 2021-08-25 |
| Start Page: | eabf5107 |
| Language: | English |
| DOI: | 10.1126/scitranslmed.abf5107 |
| PUBMED: | 34433638 |
| PROVIDER: | scopus |
| PMCID: | PMC9254663 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 1 October 2021 -- Source: Scopus |
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