LAG-3 expression on peripheral blood cells identifies patients with poorer outcomes after immune checkpoint blockade

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-tr...

Celý popis

Uložené v:
Podrobná bibliografia
Vydané v:Science translational medicine Ročník 13; číslo 608
Hlavní autori: Shen, Ronglai, Postow, Michael A, Adamow, Matthew, Arora, Arshi, Hannum, Margaret, Maher, Colleen, Wong, Phillip, Curran, Michael A, Hollmann, Travis J, Jia, Liwei, Al-Ahmadie, Hikmat, Keegan, Niamh, Funt, Samuel A, Iyer, Gopa, Rosenberg, Jonathan E, Bajorin, Dean F, Chapman, Paul B, Shoushtari, Alexander N, Betof, Allison S, Momtaz, Parisa, Merghoub, Taha, Wolchok, Jedd D, Panageas, Katherine S, Callahan, Margaret K
Médium: Journal Article
Jazyk:English
Vydavateľské údaje: United States 25.08.2021
Predmet:
Biomarkers, Tumor
Carcinoma, Transitional Cell
Humans
Immune Checkpoint Inhibitors
T-Lymphocytes
Urinary Bladder Neoplasms
ISSN:1946-6242, 1946-6242
On-line prístup:Zistit podrobnosti o prístupe
Tagy: Pridať tag
Žiadne tagy, Buďte prvý, kto otaguje tento záznam!
Popis
Shrnutí: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 ( = 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 ( = 0.007), survival ( < 0.001), and progression-free survival ( = 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.
Bibliografia:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ISSN:1946-6242
1946-6242
DOI:10.1126/scitranslmed.abf5107