Kagamu H et al. and our group recently reported the association between high levels of effector and highly differentiated CD4 T cells in peripheral blood and response to ICI in pretreated NSCLC (Zuazo M, 2019; Kagamu H, 2020). We have evaluated the dynamics of immune cell populations in patients receiving pembrolizumab as first line.
PBMCs from 25 patients with advanced NSCLC receiving pembrolizumab alone or concomitant with chemotherapy were obtained from peripheral blood before treatment. Cell subpopulations have been studied by flow cytometry according to the expression of CD3, CD4, CD8, CD11b, CD14, CD27, CD28, CD56, CD64, CD66b, CD116, CD163 and CD206.
Higher levels of CD116+ CD66b+ neutrophils (21.1% vs 3.8%, p=0.045) and CD11b+ CD56+ CD14- NK cells (22.6% vs 12.7%, p=0.003) were associated with progression, while responders had lower levels of CD4+ CD27- CD28- cells (p = 0.032). Over the mean (OTM) CD4+ CD27- CD28- and NK cell levels were associated with shorter PFS (NR vs 8.3 wk, p = 0.026 and 64.1 vs 2.9 wk, p= 0.005). OTM neutrophils were associated with shorter OS (71.7 vs 9.9 wk, p = 0.012). ROC analysis showed an association between OTM neutrophils and progression as best response (AUC 0.903, p=0.005), with a threshold of 6.2% for a 90% specificity and 75% sensitivity. A score based on OTM neutrophils, NK and CD4+ CD27- CD28- cells discriminates patients according to their mPFS (0 = 64 wk, 1 = 22.9 wk, 2-3 = 2.86 wk; p=0.029).
Pretreatment immune cell subpopulations in peripheral blood quantified by flow cytometry might be useful to predict immunotherapy efficacy. Myeloid and CD27- CD28- CD4 cells cells might play relevant role in primary resistance to ICI.
Legal entity responsible for the study
IdiSNA, Navarra Institute for Health Research.
Asociación Española Contra el Cáncer (AECC), Instituto de Salud Carlos III.
All authors have declared no conflicts of interest.