Intratumoral Versus Circulating Lymphoid Cells as Predictive Biomarkers in Lung Cancer Patients Treated with Immune Checkpoint Inhibitors: Is the Easiest Path the Best One?

Abstract

The molecular and cell determinants that modulate immune checkpoint (ICI) efficacy in lung cancer are still not well understood. However, there is a necessity to select those patients that will most benefit from these new treatments. Recent studies suggest the presence and/or the relative balance of specific lymphoid cells in the tumor microenvironment (TEM) including the T cell (activated, memory, and regulatory) and NK cell (CD56dim/bright) subsets, and correlate with a better response to ICI. The analyses of these cell subsets in peripheral blood, as a more accessible and homogeneous sample, might facilitate clinical decisions concerning fast prediction of ICI efficacy. Despite recent studies suggesting that lymphoid circulating cells might correlate with ICI efficacy and toxicity, more analyses and investigation are required to confirm if circulating lymphoid cells are a relevant picture of the lung TME and could be instrumental as ICI response biomarkers. This short review is aimed to discuss the recent advances in this fast-growing field.

Keywords: biomarkers; immune cells in cancer; immune checkpoints inhibitors; lung cancer; tumor microenvironment.

Figure 1

Biomarkers of response in TME and Peripheral blood. PD-1: Programmed Death – 1, TME: tumor microenvironment Treg: T regulatory cell, FOXP3+: Forkhead box P3, NK: Natural killers, MDSCS: myeloid-derived suppressor cells, ALC: absolute lymphocyte count, TILs: tumor infiltrating lymphocites, Trm: resident memory T cells, NLR: neutrophil to lymphocyte ratio.