The use of immune checkpoint inhibitors (ICIs) continues to transform the therapeutic landscape of non-small cell lung cancer . The importance of this cancer ‘macroenvironment can be deciphered by comprehensive analysis of peripheral blood immune cell subsets, has been demonstrated in several cutting-edge preclinical reports, and is corroborated by intriguing data emerging from ICI-treated patients . In this review, we will provide the biological rationale underlying the potential of blood . cell-based biomarkers in guiding treatment decision in immunotherapy-eligible NSCLC patients.