Peripheral blood lymphocytes differentiation patterns in responses / outcomes to immune checkpoint blockade therapies in non-small cell lung cancer: a retrospective study

Abstract

Objectives Programmed Cell Death-1/ Programmed Death-ligand 1 (PD-1 / PD-L1) inhibitor therapies targeting immunocytes induce persistent tumor remission in various cancers. However, the appropriate biomarkers for the therapeutic efficacy of PD-L1 and PD-1 blockade remain elusive. Materials and methods For a comprehensive analysis of peri-treatment lymphocyte differentiation, in the current study, we enrolled 146 non-small cell lung cancer patients who received α-PD-1 therapies for exploring the peripheral blood lymphocyte differentiation pattern at baseline and post-treatment (dynamic changes) by flow cytometry. Results At baseline, CD4+ / CD8+ T cell ratio predicts good responses and outcomes, but activated T cell and cytotoxic T cell counts predict poor responses and outcomes. And for dynamic changes, after 6 weeks of immune checkpoint blockade (ICB) treatment, compared with baseline level, the elevation of total T and B cell counts indicate poor responses, and total T and TH cell counts indicate poor prognosis while activated T cell predicts good prognosis. And after 12 weeks, elevated total lymphocyte, cytotoxic T cell counts, and decreased total T cell counts and CD4+ / CD8+ T cell ratio predict good responses / outcomes. Our clinical predicting model shows good performance in predicting ICB treatment responses / outcomes. Conclusion Patients with favorable clinical responses / outcomes have distinctive peripheral blood immunocyte differentiation characteristics, indicating the potential of utilizing the peripheral immunocyte differentiation patterns for predicting ICB responses / outcomes.

Preclinical efficacy of carfilzomib in BRAF‐mutant colorectal cancer models

“…The increased ratio of cytotoxic CD8 + T lymphocytes over FOXP3 + regulatory T cells within the tumor upon chemotherapy predict favorable therapeutic responses in many cancer types [ 54 , 55 ]. For instance, CD8 + tumor‐infiltrating lymphocytes are associated with favorable prognosis in patients with triple‐negative breast cancer [ 56 ] and non‐small cell lung cancer [ 57 ]. Interestingly, in breast or CRC patients treated with the ICD inducers anthracyclines and oxaliplatin, respectively, increased cytotoxic CD8 + T lymphocytes resulted crucial for the outcomes of therapy [ 58 ].…”

Neoadjuvant chemoradiotherapy combined with sequential perioperative toripalimab in locally advanced esophageal squamous cell cancer

“…These findings were consistent with that of some previous studies. [33][34][35] Nevertheless, these preliminary results still require confirmation in a larger population. Furthermore, it is important to thoroughly analyze the consistency of the immune cell subset compositions between peripheral blood and tumor microenvironment, as well as the specific status and function of T cell subsets.…”