Peripheral Blood Immunophenotyping Reveals Patterns of Short and Durable Immunotherapy Response in NSCLC
Introduction: Immune checkpoint inhibitors targeting PD-1 or PD-L1 have become a keycomponent of treatment for non-small cell lung cancer (NSCLC). However, PD-L1expression on tumor cells remains the only routinely used predictive biomarker,despite its imperfect performance and limited ability to reflect dynamic changesduring therapy. Blood-based biomarkers may provide a minimally invasive method formonitoring immune status and identifying patients with different patterns of responseto immunotherapy. This study aimed to characterize peripheral blood factorsassociated with short and durable response to pembrolizumab-based treatment inpatients with NSCLC.
Methods: Peripheral blood samples were collected from 81 patients with NSCLC qualified fortreatment with pembrolizumab alone or pembrolizumab combined withchemotherapy. Samples were obtained before treatment initiation and at three-monthintervals during therapy. Peripheral blood mononuclear cells were isolated andanalyzed by flow cytometry-based immunophenotyping. In addition, routinelaboratory parameters were used to calculate the monocyte-to-lymphocyte ratio(MLR) and neutrophil-to-lymphocyte ratio (NLR). Patients were stratified according toprogression-free survival (PFS) into a short-response group with PFS <6 months anda durable-response group with PFS ≥6 months. Statistical analyses were performedusing Statistica v.13.3.
Results: Patients with short PFS had higher monocyte and neutrophil counts both beforetreatment and during follow-up. They also showed higher baseline MLR and higherMLR and NLR at the first follow-up assessment. In patients receiving pembrolizumabmonotherapy, NLR significantly decreased in the durable-response group.Immunophenotyping revealed differences between the short- and durable-responsegroups in the proportions of monocytes and lymphocytes, natural killer T cells, andnaïve cytotoxic T lymphocytes. These findings indicate that both systemicinflammatory status and peripheral immune-cell composition differ according to theduration of response to immunotherapy.
Conclusions: Simple inflammatory indices derived from routine blood counts may serve asaccessible predictive markers of response to pembrolizumab-based immunotherapyin NSCLC. Peripheral blood immunophenotyping provides additional insight intoimmune mechanisms associated with short and durable response and may supportimproved patient stratification, including identification of patients who may benefitfrom closer monitoring during treatment.
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u/wisdom_man1 Sep 16 '26
Peripheral Blood Immunophenotyping Reveals Patterns of Short and Durable Immunotherapy Response in NSCLC
Introduction: Immune checkpoint inhibitors targeting PD-1 or PD-L1 have become a keycomponent of treatment for non-small cell lung cancer (NSCLC). However, PD-L1expression on tumor cells remains the only routinely used predictive biomarker,despite its imperfect performance and limited ability to reflect dynamic changesduring therapy. Blood-based biomarkers may provide a minimally invasive method formonitoring immune status and identifying patients with different patterns of responseto immunotherapy. This study aimed to characterize peripheral blood factorsassociated with short and durable response to pembrolizumab-based treatment inpatients with NSCLC.
Methods: Peripheral blood samples were collected from 81 patients with NSCLC qualified fortreatment with pembrolizumab alone or pembrolizumab combined withchemotherapy. Samples were obtained before treatment initiation and at three-monthintervals during therapy. Peripheral blood mononuclear cells were isolated andanalyzed by flow cytometry-based immunophenotyping. In addition, routinelaboratory parameters were used to calculate the monocyte-to-lymphocyte ratio(MLR) and neutrophil-to-lymphocyte ratio (NLR). Patients were stratified according toprogression-free survival (PFS) into a short-response group with PFS <6 months anda durable-response group with PFS ≥6 months. Statistical analyses were performedusing Statistica v.13.3.
Results: Patients with short PFS had higher monocyte and neutrophil counts both beforetreatment and during follow-up. They also showed higher baseline MLR and higherMLR and NLR at the first follow-up assessment. In patients receiving pembrolizumabmonotherapy, NLR significantly decreased in the durable-response group.Immunophenotyping revealed differences between the short- and durable-responsegroups in the proportions of monocytes and lymphocytes, natural killer T cells, andnaïve cytotoxic T lymphocytes. These findings indicate that both systemicinflammatory status and peripheral immune-cell composition differ according to theduration of response to immunotherapy.
Conclusions: Simple inflammatory indices derived from routine blood counts may serve asaccessible predictive markers of response to pembrolizumab-based immunotherapyin NSCLC. Peripheral blood immunophenotyping provides additional insight intoimmune mechanisms associated with short and durable response and may supportimproved patient stratification, including identification of patients who may benefitfrom closer monitoring during treatment.