Tumor mutation burden in the prognosis and response of lung cancer patients to immune-checkpoint inhibition therapies
Immune checkpoint inhibition (ICI) therapies have reshaped the therapeutic landscape in lung cancer management, providing first-time improvements in patient response, prognosis, and overall survival. Despite their clinical effectiveness, variability in treatment responsiveness, as well as drug resis...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-12-01
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| Series: | Translational Oncology |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1936523323001742 |
| _version_ | 1797657861690490880 |
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| author | Paraskevi Vryza Timo Fischer Elena Mistakidi Apostolos Zaravinos |
| author_facet | Paraskevi Vryza Timo Fischer Elena Mistakidi Apostolos Zaravinos |
| author_sort | Paraskevi Vryza |
| collection | DOAJ |
| description | Immune checkpoint inhibition (ICI) therapies have reshaped the therapeutic landscape in lung cancer management, providing first-time improvements in patient response, prognosis, and overall survival. Despite their clinical effectiveness, variability in treatment responsiveness, as well as drug resistance, have led to a compelling need for predictive biomarkers facilitating the individualized selection of the most efficient therapeutic approach. Significant progress has been made in the identification of such biomarkers, with tumor mutation burden (ΤΜΒ) appearing as the leading and most promising predictive biomarker for the efficacy of ICIs in non-small cell lung cancer (NSCLC) among other tumors. Anti-PD-1/PD-L1 and anti-CTLA-4 antibodies have been extensively studied and clinically utilized. However, the overall efficiency of these drugs remains unsatisfactory, urging for the investigation of novel inhibitors, such as those targeting LAG-3, TIM-3, TIGIT and VISTA, which could be used either as a monotherapy or synergistically with the PD-1/PD-L1 or CTLA-4 blockers. Here, we investigate the role of TMB and cancer neoantigens as predictive biomarkers in the response of lung cancer patients to different ICI therapies, specifically focusing on the most recent immune checkpoint inhibitors, against LAG-3, TIM-3, TIGIT and VISTA. We further discuss the new trends in immunotherapies, including CAR T-cell therapy and personalized tumor vaccines. We also review further potential biomarkers that could be used in lung cancer response to immunotherapy, such as PD-L1+ IHC, MSI/dMMR, tumor infiltrating lymphocytes (TILs), as well as the role of the microbiome and circulating tumor DNA (ctDNA). Finally, we discuss the limitations and challenges of each. |
| first_indexed | 2024-03-11T17:50:42Z |
| format | Article |
| id | doaj.art-23586e0a706840cdad5d37bea8ab5c78 |
| institution | Directory Open Access Journal |
| issn | 1936-5233 |
| language | English |
| last_indexed | 2024-03-11T17:50:42Z |
| publishDate | 2023-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Translational Oncology |
| spelling | doaj.art-23586e0a706840cdad5d37bea8ab5c782023-10-18T04:30:55ZengElsevierTranslational Oncology1936-52332023-12-0138101788Tumor mutation burden in the prognosis and response of lung cancer patients to immune-checkpoint inhibition therapiesParaskevi Vryza0Timo Fischer1Elena Mistakidi2Apostolos Zaravinos3School of Medicine, European University Cyprus, Nicosia 1516, Cyprus; Cancer Genetics, Genomics and Systems Biology Laboratory, Basic and Translational Cancer Research Center (BTCRC), Nicosia 1516, CyprusSchool of Medicine, European University Cyprus, Nicosia 1516, Cyprus; Cancer Genetics, Genomics and Systems Biology Laboratory, Basic and Translational Cancer Research Center (BTCRC), Nicosia 1516, CyprusSchool of Medicine, European University Cyprus, Nicosia 1516, Cyprus; Cancer Genetics, Genomics and Systems Biology Laboratory, Basic and Translational Cancer Research Center (BTCRC), Nicosia 1516, CyprusCancer Genetics, Genomics and Systems Biology Laboratory, Basic and Translational Cancer Research Center (BTCRC), Nicosia 1516, Cyprus; Department of Life Sciences, School of Sciences, European University Cyprus, Nicosia 1516, Cyprus; Corresponding author at: Department of Life Sciences, School of Sciences, European University Cyprus, Nicosia 1516, Cyprus.Immune checkpoint inhibition (ICI) therapies have reshaped the therapeutic landscape in lung cancer management, providing first-time improvements in patient response, prognosis, and overall survival. Despite their clinical effectiveness, variability in treatment responsiveness, as well as drug resistance, have led to a compelling need for predictive biomarkers facilitating the individualized selection of the most efficient therapeutic approach. Significant progress has been made in the identification of such biomarkers, with tumor mutation burden (ΤΜΒ) appearing as the leading and most promising predictive biomarker for the efficacy of ICIs in non-small cell lung cancer (NSCLC) among other tumors. Anti-PD-1/PD-L1 and anti-CTLA-4 antibodies have been extensively studied and clinically utilized. However, the overall efficiency of these drugs remains unsatisfactory, urging for the investigation of novel inhibitors, such as those targeting LAG-3, TIM-3, TIGIT and VISTA, which could be used either as a monotherapy or synergistically with the PD-1/PD-L1 or CTLA-4 blockers. Here, we investigate the role of TMB and cancer neoantigens as predictive biomarkers in the response of lung cancer patients to different ICI therapies, specifically focusing on the most recent immune checkpoint inhibitors, against LAG-3, TIM-3, TIGIT and VISTA. We further discuss the new trends in immunotherapies, including CAR T-cell therapy and personalized tumor vaccines. We also review further potential biomarkers that could be used in lung cancer response to immunotherapy, such as PD-L1+ IHC, MSI/dMMR, tumor infiltrating lymphocytes (TILs), as well as the role of the microbiome and circulating tumor DNA (ctDNA). Finally, we discuss the limitations and challenges of each.http://www.sciencedirect.com/science/article/pii/S1936523323001742Tumor mutation burden (TMB)Immune checkpoint inhibition therapyPatient responseTumor-infiltrating lymphocytesTumor microenvironment |
| spellingShingle | Paraskevi Vryza Timo Fischer Elena Mistakidi Apostolos Zaravinos Tumor mutation burden in the prognosis and response of lung cancer patients to immune-checkpoint inhibition therapies Translational Oncology Tumor mutation burden (TMB) Immune checkpoint inhibition therapy Patient response Tumor-infiltrating lymphocytes Tumor microenvironment |
| title | Tumor mutation burden in the prognosis and response of lung cancer patients to immune-checkpoint inhibition therapies |
| title_full | Tumor mutation burden in the prognosis and response of lung cancer patients to immune-checkpoint inhibition therapies |
| title_fullStr | Tumor mutation burden in the prognosis and response of lung cancer patients to immune-checkpoint inhibition therapies |
| title_full_unstemmed | Tumor mutation burden in the prognosis and response of lung cancer patients to immune-checkpoint inhibition therapies |
| title_short | Tumor mutation burden in the prognosis and response of lung cancer patients to immune-checkpoint inhibition therapies |
| title_sort | tumor mutation burden in the prognosis and response of lung cancer patients to immune checkpoint inhibition therapies |
| topic | Tumor mutation burden (TMB) Immune checkpoint inhibition therapy Patient response Tumor-infiltrating lymphocytes Tumor microenvironment |
| url | http://www.sciencedirect.com/science/article/pii/S1936523323001742 |
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