Peripheral CD8+CD28+ T lymphocytes predict the efficacy and safety of PD-1/PD-L1 inhibitors in cancer patients

Abstract

BackgroundProgrammed cell death protein-1/programmed cell death ligand-1 (PD-1/PD-L1) inhibitors works by reactivating immune cells. Considering the accessibility of noninvasive liquid biopsies, it is advisable to employ peripheral blood lymphocyte subsets to predict immunotherapy outcomes.MethodsWe retrospectively enrolled 87 patients with available baseline circulating lymphocyte subset data who received first-line PD-1/PD-L1 inhibitors at Peking Union Medical College Hospital between May 2018 and April 2022. Immune cell counts were determined by flow cytometry.ResultsPatients who responded to PD-1/PD-L1 inhibitors had significantly higher circulating CD8+CD28+ T-cell counts (median [range] count: 236 [30-536] versus 138 [36-460]/μL, p < 0.001). Using 190/μL as the cutoff value, the sensitivity and specificity of CD8+CD28+ T cells for predicting immunotherapy response were 0.689 and 0.714, respectively. Furthermore, the median progression-free survival (PFS, not reached versus 8.7 months, p < 0.001) and overall survival (OS, not reached versus 16.2 months, p < 0.001) were significantly longer in the patients with higher CD8+CD28+ T-cell counts. However, the CD8+CD28+ T-cell level was also associated with the incidence of grade 3-4 immune-related adverse events (irAEs). The sensitivity and specificity of CD8+CD28+ T cells for predicting irAEs of grade 3-4 were 0.846 and 0.667, respectively, at the threshold of CD8+CD28+ T cells ≥ 309/μL.ConclusionsHigh circulating CD8+CD28+ T-cell levels is a potential biomarker for immunotherapy response and better prognosis, while excessive CD8+CD28+ T cells (≥ 309/μL) may also indicate the emergence of severe irAEs.

Association of immune cells and the risk of esophageal cancer: A Mendelian randomization study in a East Asian population

“…Moreover, numerous studies have indicated that immune cell phenotypes can serve as central biomarkers for immunotherapy. [ 49 , 59 , 68 – 70 ] Therefore, the 15 negative immune phenotypes we analyzed in our research may be essential biomarkers supporting immunotherapy.…”

Peripheral Blood CD8+ CD28+ T Cells as an Independent Predictor of Treatment Response and Survival After Concurrent Chemoradiotherapy in Pediatric High-Grade Glioma Patients

“…Elevated levels of circulating CD8 + CD28 + T cells are a potential biomarker for immunotherapy response and better prognosis. 31 CD28 is involved as the receptor for the second signal of T-cell activation and is a marker for an effector memory population of T cells following adoptive transfer. 14 …”

Circulating T cells: a promising biomarker of anti-PD-(L)1 therapy

“…Tem cells have been extensively studied as predictive markers of the baseline response to anti-PD-(L)1 therapy in patients with NSCLC ( 14 , 15 ). Recent studies have demonstrated that anti-PD-(L)1 therapy does not reverse the phenotype of terminally exhausted T cells but promotes the differentiation of self-renewing progenitor T cells into newly formed effector-like T cells, including memory T cells ( 37 ).…”

“…Using 190/μL as the cut-off, patients with higher CD8 + CD28 + T cell counts exhibited significantly prolonged median PFS than patients with lower counts (not reached vs. 8.7 months, p < 0.001). In addition, they had a significantly extended overall survival (OS) (not reached vs. 16.2 months, p < 0.001) ( 15 ). These findings suggest that Tem cells are strongly associated with response to PD(L)1 therapy.…”

“…Peripheral effector PD1 low CD8 + T cells exhibit an “effector-like” phenotype ( 32 ). Current evidence has revealed the response of peripheral circulating CD8 + Teff cells in patients with tumors to anti-PD-(L)1 therapy and their value in predicting the prognosis of patients with cancer ( 15 , 26 , 28 , 29 , 31 , 49 ).…”