Current Insights into the Role of Peripheral Blood Immune Cell Phenotypes in Resistance to Cancer Therapies.

Peripheral blood mononuclear cell (PBMC) immunophenotyping has emerged as a promising non-invasive approach to characterize systemic immune alterations in cancer and to identify biomarkers associated with treatment response and resistance. However, current evidence remains fragmented and predominantly descriptive, with substantial heterogeneity in study design, immunophenotyping methodologies, and patient populations, limiting the identification of robust and clinically translatable immune signatures. In this review, we aim to comprehensively analyze PBMC immune phenotypes across multiple cancer types, with particular emphasis on their association with disease progression, therapeutic outcomes, and the key methodological and translational challenges that currently limit their clinical implementation. Across malignancies, conserved immune features are consistently observed, including T cell exhaustion, regulatory T cell (Treg) expansion, and upregulation of immune checkpoint molecules, reflecting chronic immune activation and dysfunction. In parallel, tumor-specific phenotype, such as peripheral helper T (Tph) cell expansion in non-small cell lung cancer, Vδ1