Early changes of peripheral circulating immune subsets induced by PD-1 inhibitors in patients with advanced malignant melanoma and non-small cell lung cancer
Abstract 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...
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2024-12-01
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| Online Access: | https://doi.org/10.1186/s12885-024-13351-x |
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| author | Simona Borilova Peter Grell Iveta Selingerova Lenka Gescheidtova Marie Mlnarikova Ondrej Bilek Radek Lakomy Alexandr Poprach Jan Podhorec Igor Kiss Rostislav Vyzula Barbora Vavrusakova Jiri Nevrlka Lenka Zdrazilova-Dubska |
| author_facet | Simona Borilova Peter Grell Iveta Selingerova Lenka Gescheidtova Marie Mlnarikova Ondrej Bilek Radek Lakomy Alexandr Poprach Jan Podhorec Igor Kiss Rostislav Vyzula Barbora Vavrusakova Jiri Nevrlka Lenka Zdrazilova-Dubska |
| author_sort | Simona Borilova |
| collection | DOAJ |
| description | Abstract 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. |
| format | Article |
| id | doaj-art-81c82e8943d1461ca344873d4e5f821d |
| institution | Kabale University |
| issn | 1471-2407 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | BMC |
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| series | BMC Cancer |
| spelling | doaj-art-81c82e8943d1461ca344873d4e5f821d2025-01-05T12:33:08ZengBMCBMC Cancer1471-24072024-12-0124111310.1186/s12885-024-13351-xEarly changes of peripheral circulating immune subsets induced by PD-1 inhibitors in patients with advanced malignant melanoma and non-small cell lung cancerSimona Borilova0Peter Grell1Iveta Selingerova2Lenka Gescheidtova3Marie Mlnarikova4Ondrej Bilek5Radek Lakomy6Alexandr Poprach7Jan Podhorec8Igor Kiss9Rostislav Vyzula10Barbora Vavrusakova11Jiri Nevrlka12Lenka Zdrazilova-Dubska13Department of Comprehensive Cancer Care, Masaryk Memorial Cancer InstituteDepartment of Comprehensive Cancer Care, Masaryk Memorial Cancer InstituteDepartment of Laboratory Medicine, Masaryk Memorial Cancer InstituteDepartment of Laboratory Medicine, Masaryk Memorial Cancer InstituteDepartment of Pharmacology, Faculty of Medicine, Masaryk UniversityDepartment of Comprehensive Cancer Care, Masaryk Memorial Cancer InstituteDepartment of Comprehensive Cancer Care, Masaryk Memorial Cancer InstituteDepartment of Comprehensive Cancer Care, Masaryk Memorial Cancer InstituteDepartment of Comprehensive Cancer Care, Masaryk Memorial Cancer InstituteDepartment of Comprehensive Cancer Care, Masaryk Memorial Cancer InstituteDepartment of Comprehensive Cancer Care, Masaryk Memorial Cancer InstituteResearch Center for Applied Molecular Oncology (RECAMO), Masaryk Memorial Cancer InstituteDepartment of Pharmacology, Faculty of Medicine, Masaryk UniversityDepartment of Pharmacology, Faculty of Medicine, Masaryk UniversityAbstract 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.https://doi.org/10.1186/s12885-024-13351-xImmune checkpoint inhibitorsAntitumor immunityPredictive biomarkerPeripheral blood circulating immune subsets |
| spellingShingle | Simona Borilova Peter Grell Iveta Selingerova Lenka Gescheidtova Marie Mlnarikova Ondrej Bilek Radek Lakomy Alexandr Poprach Jan Podhorec Igor Kiss Rostislav Vyzula Barbora Vavrusakova Jiri Nevrlka Lenka Zdrazilova-Dubska Early changes of peripheral circulating immune subsets induced by PD-1 inhibitors in patients with advanced malignant melanoma and non-small cell lung cancer BMC Cancer Immune checkpoint inhibitors Antitumor immunity Predictive biomarker Peripheral blood circulating immune subsets |
| title | Early changes of peripheral circulating immune subsets induced by PD-1 inhibitors in patients with advanced malignant melanoma and non-small cell lung cancer |
| title_full | Early changes of peripheral circulating immune subsets induced by PD-1 inhibitors in patients with advanced malignant melanoma and non-small cell lung cancer |
| title_fullStr | Early changes of peripheral circulating immune subsets induced by PD-1 inhibitors in patients with advanced malignant melanoma and non-small cell lung cancer |
| title_full_unstemmed | Early changes of peripheral circulating immune subsets induced by PD-1 inhibitors in patients with advanced malignant melanoma and non-small cell lung cancer |
| title_short | Early changes of peripheral circulating immune subsets induced by PD-1 inhibitors in patients with advanced malignant melanoma and non-small cell lung cancer |
| title_sort | early changes of peripheral circulating immune subsets induced by pd 1 inhibitors in patients with advanced malignant melanoma and non small cell lung cancer |
| topic | Immune checkpoint inhibitors Antitumor immunity Predictive biomarker Peripheral blood circulating immune subsets |
| url | https://doi.org/10.1186/s12885-024-13351-x |
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