Přehled o publikaci
2024
Early changes of peripheral circulating immune subsets induced by PD-1 inhibitors in patients with advanced malignant melanoma and non-small cell lung cancer
BOŘILOVÁ, Simona, Peter GRELL, Iveta SELINGEROVÁ, Lenka GESCHEIDTOVÁ, Marie MLNAŘÍKOVÁ et. al.Basic information
Original name
Early changes of peripheral circulating immune subsets induced by PD-1 inhibitors in patients with advanced malignant melanoma and non-small cell lung cancer
Authors
BOŘILOVÁ, Simona, Peter GRELL, Iveta SELINGEROVÁ, Lenka GESCHEIDTOVÁ, Marie MLNAŘÍKOVÁ, Ondřej BÍLEK, Radek LAKOMÝ, Alexandr POPRACH, Ján PODHOREC, Igor KISS, Rostislav VYZULA, Barbora VAVRUŠÁKOVÁ, Jiří NEVRLKA and Lenka ZDRAŽILOVÁ DUBSKÁ
Edition
BMC Cancer, London, UK, BioMed Central, 2024, 1471-2407
Other information
Language
English
Type of outcome
Article in a journal
Country of publisher
United Kingdom of Great Britain and Northern Ireland
Confidentiality degree
is not subject to a state or trade secret
References:
Organization
Lékařská fakulta – Repository – Repository
UT WoS
001389279700008
EID Scopus
2-s2.0-85213692471
Keywords in English
Immune checkpoint inhibitors; Antitumor immunity; Predictive biomarker; Peripheral blood circulating immune subsets
Links
LX22NPO5102, research and development project. MUNI/A/1580/2023, interní kód Repo. NU21-03-00539, research and development project.
Changed: 4/3/2025 00:51, RNDr. Daniel Jakubík
Abstract
V originále
Background Immune checkpoint inhibitors (ICIs), including those targeting PD-1, are currently used in a wide range of tumors, but only 20–40% of patients achieve clinical benefit. The objective of our study was to find predictive peripheral blood-based biomarkers for ICI treatment. Methods In 41 patients with advanced malignant melanoma (MM) and NSCLC treated with PD-1 inhibitors, we analyzed peripheral blood-based immune subsets by flow cytometry before treatment initialization and the second therapy dose. Specifically, we assessed basic blood differential count, overall T cells and their subgroups, B cells, and myeloid-derived suppressor cells (MDSC). In detail, CD4 + and CD8 + T cells were assessed according to their subtypes, such as central memory T cells (TCM), effector memory T cells (TEM), and naïve T cells (TN). Furthermore, we also evaluated the predictive value of CD28 and ICOS/CD278 co-expression on T cells. Results Patients who achieved disease control on ICIs had a significantly lower baseline proportion of CD4 + TEM (p = 0.013) and tended to have a higher baseline proportion of CD4 + TCM (p = 0.059). ICI therapy-induced increase in Treg count (p = 0.012) and the proportion of CD4 + TN (p = 0.008) and CD28 + ICOS- T cells (p = 0.012) was associated with disease control. Patients with a high baseline proportion of CD4 + TCM and a low baseline proportion of CD4 + TEM showed significantly longer PFS (p = 0.011, HR 2.6 and p ˂ 0.001, HR 0.23, respectively) and longer OS (p = 0.002, HR 3.75 and p ˂ 0.001, HR 0.15, respectively). Before the second dose, the high proportion of CD28 + ICOS- T cells after ICI therapy initiation was significantly associated with prolonged PFS (p = 0.017, HR 2.51) and OS (p = 0.030, HR 2.69). Also, a high Treg count after 2 weeks of ICI treatment was associated with significantly prolonged PFS (p = 0.016, HR 2.33) Conclusion In summary, our findings suggest that CD4 + TEM and TCM baselines and an early increase in the Treg count induced by PD-1 inhibitors and the proportion of CD28 + ICOS- T cells may be useful in predicting the response in NSCLC and MM patients.
