CD137+ and regulatory T cells as independent prognostic factors of survival in advanced non-oncogene addicted NSCLC patients treated with immunotherapy as first-line
Abstract Background Immune checkpoint inhibitors (ICIs), administered alone or combined with chemotherapy, are the standard of care in advanced non-oncogene addicted Non-Small Cell Lung Cancer (NSCLC). Despite these treatments' success, most long-term survival benefit is restricted to approxima...
| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2024-04-01
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| Series: | Journal of Translational Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12967-024-05142-6 |
| _version_ | 1797219584138280960 |
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| author | Alain Gelibter Angela Asquino Lidia Strigari Ilaria Grazia Zizzari Lucrezia Tuosto Fabio Scirocchi Angelica Pace Marco Siringo Elisa Tramontano Serena Bianchini Filippo Bellati Andrea Botticelli Donatella Paoli Daniele Santini Marianna Nuti Aurelia Rughetti Chiara Napoletano |
| author_facet | Alain Gelibter Angela Asquino Lidia Strigari Ilaria Grazia Zizzari Lucrezia Tuosto Fabio Scirocchi Angelica Pace Marco Siringo Elisa Tramontano Serena Bianchini Filippo Bellati Andrea Botticelli Donatella Paoli Daniele Santini Marianna Nuti Aurelia Rughetti Chiara Napoletano |
| author_sort | Alain Gelibter |
| collection | DOAJ |
| description | Abstract Background Immune checkpoint inhibitors (ICIs), administered alone or combined with chemotherapy, are the standard of care in advanced non-oncogene addicted Non-Small Cell Lung Cancer (NSCLC). Despite these treatments' success, most long-term survival benefit is restricted to approximately 20% of patients, highlighting the need to identify novel biomarkers to optimize treatment strategies. In several solid tumors, immune soluble factors, the activatory CD137+ Tcells, and the immunosuppressive cell subsets Tregs and MDSCs (PMN(Lox1+)-MDSC and M-MDSCs) correlated with responses to ICIs and clinical outcomes thus becoming appealing predictive and prognostic factors. This study investigated the role of distinct CD137+ Tcell subsets, Tregs, MDSCs, and immune-soluble factors in NSCLC patients as possible biomarkers. Methods The levels of T cells, MDSCs and soluble factors were evaluated in 89 metastatic NSCLC patients who underwent ICIs as first- or second-line treatment. T cell analysis was performed by cytoflurimetry evaluating Tregs and different CD137+ Tcell subsets also combined with CD3+, CD8+, PD1+, and Ki67+ markers. Circulating cytokines and immune checkpoints were also evaluated by Luminex analysis. All these parameters were correlated with several clinical factors (age, sex, smoking status, PS and TPS), response to therapy, PFS , and OS . The analyses were conducted in the overall population and in patients treated with ICIs as first-line (naïve patients). Results In both groups of patients, high levels of circulating CD137+ and CD137+PD1+ T cells (total, CD4 and CD8) and the soluble factor LAG3 positively correlated with response to therapy. In naïve patients, PMN(Lox1+)-MDSCs negatively correlated with clinical response, and a high percentage of Tregs was associated with favorable survival. Moreover, the balance between Treg/CD137+ Tcells or PMN(Lox1+)-MDSC/CD137+ Tcells was higher in non-responding patients and was associated with poor survival. CD137+ Tcells and Tregs resulted as two positive independent prognostic factors. Conclusion High levels of CD137+, CD137+PD1+ Tcells and sLAG3 could predict the response to ICIs in NSCLC patients independently by previous therapy. Combining the evaluation of CD137+ Tcells and Tregs also as Treg/CD137+ T cells ratio it is possible to identify naive patients with longer survival. |
| first_indexed | 2024-04-24T12:35:58Z |
| format | Article |
| id | doaj.art-3b1cd664555b4d159dbbfd800c53dc3b |
| institution | Directory Open Access Journal |
| issn | 1479-5876 |
| language | English |
| last_indexed | 2024-04-24T12:35:58Z |
| publishDate | 2024-04-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Translational Medicine |
| spelling | doaj.art-3b1cd664555b4d159dbbfd800c53dc3b2024-04-07T11:28:42ZengBMCJournal of Translational Medicine1479-58762024-04-0122111610.1186/s12967-024-05142-6CD137+ and regulatory T cells as independent prognostic factors of survival in advanced non-oncogene addicted NSCLC patients treated with immunotherapy as first-lineAlain Gelibter0Angela Asquino1Lidia Strigari2Ilaria Grazia Zizzari3Lucrezia Tuosto4Fabio Scirocchi5Angelica Pace6Marco Siringo7Elisa Tramontano8Serena Bianchini9Filippo Bellati10Andrea Botticelli11Donatella Paoli12Daniele Santini13Marianna Nuti14Aurelia Rughetti15Chiara Napoletano16Division of Oncology, Department of Radiological, Oncological and Pathological Science, Policlinico Umberto I, “Sapienza” University of RomeLaboratory of Tumor Immunology and Cell Therapies, Department of Experimental Medicine, Sapienza University of RomeDepartment of Medical Physics, IRCCS Azienda Ospedaliera-Universitaria Di BolognaLaboratory of Tumor Immunology and Cell Therapies, Department of Experimental Medicine, Sapienza University of RomeLaboratory of Tumor Immunology and Cell Therapies, Department of Experimental Medicine, Sapienza University of RomeLaboratory of Tumor Immunology and Cell Therapies, Department of Experimental Medicine, Sapienza University of RomeLaboratory of Tumor Immunology and Cell Therapies, Department of Experimental Medicine, Sapienza University of RomeDivision of Oncology, Department of Radiological, Oncological and Pathological Science, Policlinico Umberto I, “Sapienza” University of RomeDivision of Oncology, Department of Radiological, Oncological and Pathological Science, Policlinico Umberto I, “Sapienza” University of RomeLaboratory of Seminology-Sperm Bank “Loredana Gandini”, Department of Experimental Medicine, “Sapienza” University of RomeDepartment of Medical and Surgical Sciences and Translational Medicine, Sant’Andrea University Hospital, Sapienza University of RomeDivision of Oncology, Department of Radiological, Oncological and Pathological Science, Policlinico Umberto I, “Sapienza” University of RomeLaboratory of Seminology-Sperm Bank “Loredana Gandini”, Department of Experimental Medicine, “Sapienza” University of RomeDivision of Oncology, Department of Radiological, Oncological and Pathological Science, Policlinico Umberto I, “Sapienza” University of RomeLaboratory of Tumor Immunology and Cell Therapies, Department of Experimental Medicine, Sapienza University of RomeLaboratory of Tumor Immunology and Cell Therapies, Department of Experimental Medicine, Sapienza University of RomeLaboratory of Tumor Immunology and Cell Therapies, Department of Experimental Medicine, Sapienza University of RomeAbstract Background Immune checkpoint inhibitors (ICIs), administered alone or combined with chemotherapy, are the standard of care in advanced non-oncogene addicted Non-Small Cell Lung Cancer (NSCLC). Despite these treatments' success, most long-term survival benefit is restricted to approximately 20% of patients, highlighting the need to identify novel biomarkers to optimize treatment strategies. In several solid tumors, immune soluble factors, the activatory CD137+ Tcells, and the immunosuppressive cell subsets Tregs and MDSCs (PMN(Lox1+)-MDSC and M-MDSCs) correlated with responses to ICIs and clinical outcomes thus becoming appealing predictive and prognostic factors. This study investigated the role of distinct CD137+ Tcell subsets, Tregs, MDSCs, and immune-soluble factors in NSCLC patients as possible biomarkers. Methods The levels of T cells, MDSCs and soluble factors were evaluated in 89 metastatic NSCLC patients who underwent ICIs as first- or second-line treatment. T cell analysis was performed by cytoflurimetry evaluating Tregs and different CD137+ Tcell subsets also combined with CD3+, CD8+, PD1+, and Ki67+ markers. Circulating cytokines and immune checkpoints were also evaluated by Luminex analysis. All these parameters were correlated with several clinical factors (age, sex, smoking status, PS and TPS), response to therapy, PFS , and OS . The analyses were conducted in the overall population and in patients treated with ICIs as first-line (naïve patients). Results In both groups of patients, high levels of circulating CD137+ and CD137+PD1+ T cells (total, CD4 and CD8) and the soluble factor LAG3 positively correlated with response to therapy. In naïve patients, PMN(Lox1+)-MDSCs negatively correlated with clinical response, and a high percentage of Tregs was associated with favorable survival. Moreover, the balance between Treg/CD137+ Tcells or PMN(Lox1+)-MDSC/CD137+ Tcells was higher in non-responding patients and was associated with poor survival. CD137+ Tcells and Tregs resulted as two positive independent prognostic factors. Conclusion High levels of CD137+, CD137+PD1+ Tcells and sLAG3 could predict the response to ICIs in NSCLC patients independently by previous therapy. Combining the evaluation of CD137+ Tcells and Tregs also as Treg/CD137+ T cells ratio it is possible to identify naive patients with longer survival.https://doi.org/10.1186/s12967-024-05142-6NSCLCImmune checkpoint inhibitorsPembrolizumabImmunotherapyCD137+ T cellsTregs |
| spellingShingle | Alain Gelibter Angela Asquino Lidia Strigari Ilaria Grazia Zizzari Lucrezia Tuosto Fabio Scirocchi Angelica Pace Marco Siringo Elisa Tramontano Serena Bianchini Filippo Bellati Andrea Botticelli Donatella Paoli Daniele Santini Marianna Nuti Aurelia Rughetti Chiara Napoletano CD137+ and regulatory T cells as independent prognostic factors of survival in advanced non-oncogene addicted NSCLC patients treated with immunotherapy as first-line Journal of Translational Medicine NSCLC Immune checkpoint inhibitors Pembrolizumab Immunotherapy CD137+ T cells Tregs |
| title | CD137+ and regulatory T cells as independent prognostic factors of survival in advanced non-oncogene addicted NSCLC patients treated with immunotherapy as first-line |
| title_full | CD137+ and regulatory T cells as independent prognostic factors of survival in advanced non-oncogene addicted NSCLC patients treated with immunotherapy as first-line |
| title_fullStr | CD137+ and regulatory T cells as independent prognostic factors of survival in advanced non-oncogene addicted NSCLC patients treated with immunotherapy as first-line |
| title_full_unstemmed | CD137+ and regulatory T cells as independent prognostic factors of survival in advanced non-oncogene addicted NSCLC patients treated with immunotherapy as first-line |
| title_short | CD137+ and regulatory T cells as independent prognostic factors of survival in advanced non-oncogene addicted NSCLC patients treated with immunotherapy as first-line |
| title_sort | cd137 and regulatory t cells as independent prognostic factors of survival in advanced non oncogene addicted nsclc patients treated with immunotherapy as first line |
| topic | NSCLC Immune checkpoint inhibitors Pembrolizumab Immunotherapy CD137+ T cells Tregs |
| url | https://doi.org/10.1186/s12967-024-05142-6 |
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