Biomarkers in immune checkpoint inhibition therapy for cancer patients: what is the role of lymphocyte subsets and PD1/PD-L1?
Abstract Although durable clinical responses are achieved in a significant number of patients given Immune checkpoint inhibitors (ICI), like anti-CTLA-4 and anti-PD-1 inhibitors, some of the cancers have shown little or no response to ICI therapy. Even within the known responsive cancers, there is o...
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| Format: | Article |
| Language: | English |
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BMC
2019-02-01
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| Series: | Translational Medicine Communications |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s41231-019-0032-9 |
| _version_ | 1818469325724450816 |
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| author | Puneet Singh Paul de Souza Kieran F. Scott Bruce M. Hall Nirupama D. Verma Therese M. Becker James W. T. Toh Mila Sajinovic Kevin J. Spring |
| author_facet | Puneet Singh Paul de Souza Kieran F. Scott Bruce M. Hall Nirupama D. Verma Therese M. Becker James W. T. Toh Mila Sajinovic Kevin J. Spring |
| author_sort | Puneet Singh |
| collection | DOAJ |
| description | Abstract Although durable clinical responses are achieved in a significant number of patients given Immune checkpoint inhibitors (ICI), like anti-CTLA-4 and anti-PD-1 inhibitors, some of the cancers have shown little or no response to ICI therapy. Even within the known responsive cancers, there is often a subset of non-responsive patients. Due to the accelerated FDA approval of these immunotherapies, the biomarker development has not been able to keep pace. Appropriate predictive, prognostic and surrogate biomarkers are needed to maximally exploit the benefits from ICI therapy for correct and timely stratification of patients to treatment, for monitoring treatment effect, and for avoiding costs and unwanted toxicities when therapy is likely to be ineffective. As the number of clinical trials exploring the utility of these treatments, both as stand-alone and as combination therapy for several cancers is escalating dramatically, the need for appropriate biomarkers is further amplified. This review discusses the potential biomarkers being investigated in ICI therapies, focusing mainly on immunohistochemical expression of PDL-1 and the immune correlates. Various immune components discussed here include the cells of innate (natural killer or NK cells) and adaptive (CD4+ and CD8+ cells) immunity, regulatory and inhibitory immune cells (regulatory T cells or Tregs and myeloid derived suppressor cells or MDSCs), as well as cytokines. Immune checkpoint molecule, programmed death receptor ligand-1 (PD-L1) and various molecules and pathways influencing its expression are also discussed. |
| first_indexed | 2024-04-13T21:22:10Z |
| format | Article |
| id | doaj.art-5e7bfbc3b7b54f42ba821c6a42ac4cb0 |
| institution | Directory Open Access Journal |
| issn | 2396-832X |
| language | English |
| last_indexed | 2024-04-13T21:22:10Z |
| publishDate | 2019-02-01 |
| publisher | BMC |
| record_format | Article |
| series | Translational Medicine Communications |
| spelling | doaj.art-5e7bfbc3b7b54f42ba821c6a42ac4cb02022-12-22T02:29:27ZengBMCTranslational Medicine Communications2396-832X2019-02-014111310.1186/s41231-019-0032-9Biomarkers in immune checkpoint inhibition therapy for cancer patients: what is the role of lymphocyte subsets and PD1/PD-L1?Puneet Singh0Paul de Souza1Kieran F. Scott2Bruce M. Hall3Nirupama D. Verma4Therese M. Becker5James W. T. Toh6Mila Sajinovic7Kevin J. Spring8The Ingham Institute for Applied Medical ResearchThe Ingham Institute for Applied Medical ResearchThe Ingham Institute for Applied Medical ResearchThe Ingham Institute for Applied Medical ResearchThe Ingham Institute for Applied Medical ResearchThe Ingham Institute for Applied Medical ResearchThe Ingham Institute for Applied Medical ResearchThe Ingham Institute for Applied Medical ResearchThe Ingham Institute for Applied Medical ResearchAbstract Although durable clinical responses are achieved in a significant number of patients given Immune checkpoint inhibitors (ICI), like anti-CTLA-4 and anti-PD-1 inhibitors, some of the cancers have shown little or no response to ICI therapy. Even within the known responsive cancers, there is often a subset of non-responsive patients. Due to the accelerated FDA approval of these immunotherapies, the biomarker development has not been able to keep pace. Appropriate predictive, prognostic and surrogate biomarkers are needed to maximally exploit the benefits from ICI therapy for correct and timely stratification of patients to treatment, for monitoring treatment effect, and for avoiding costs and unwanted toxicities when therapy is likely to be ineffective. As the number of clinical trials exploring the utility of these treatments, both as stand-alone and as combination therapy for several cancers is escalating dramatically, the need for appropriate biomarkers is further amplified. This review discusses the potential biomarkers being investigated in ICI therapies, focusing mainly on immunohistochemical expression of PDL-1 and the immune correlates. Various immune components discussed here include the cells of innate (natural killer or NK cells) and adaptive (CD4+ and CD8+ cells) immunity, regulatory and inhibitory immune cells (regulatory T cells or Tregs and myeloid derived suppressor cells or MDSCs), as well as cytokines. Immune checkpoint molecule, programmed death receptor ligand-1 (PD-L1) and various molecules and pathways influencing its expression are also discussed.http://link.springer.com/article/10.1186/s41231-019-0032-9CTLA-4PD-L1PD-1Immune checkpoint inhibitor therapiesImmunotherapiesBiomarkers |
| spellingShingle | Puneet Singh Paul de Souza Kieran F. Scott Bruce M. Hall Nirupama D. Verma Therese M. Becker James W. T. Toh Mila Sajinovic Kevin J. Spring Biomarkers in immune checkpoint inhibition therapy for cancer patients: what is the role of lymphocyte subsets and PD1/PD-L1? Translational Medicine Communications CTLA-4 PD-L1 PD-1 Immune checkpoint inhibitor therapies Immunotherapies Biomarkers |
| title | Biomarkers in immune checkpoint inhibition therapy for cancer patients: what is the role of lymphocyte subsets and PD1/PD-L1? |
| title_full | Biomarkers in immune checkpoint inhibition therapy for cancer patients: what is the role of lymphocyte subsets and PD1/PD-L1? |
| title_fullStr | Biomarkers in immune checkpoint inhibition therapy for cancer patients: what is the role of lymphocyte subsets and PD1/PD-L1? |
| title_full_unstemmed | Biomarkers in immune checkpoint inhibition therapy for cancer patients: what is the role of lymphocyte subsets and PD1/PD-L1? |
| title_short | Biomarkers in immune checkpoint inhibition therapy for cancer patients: what is the role of lymphocyte subsets and PD1/PD-L1? |
| title_sort | biomarkers in immune checkpoint inhibition therapy for cancer patients what is the role of lymphocyte subsets and pd1 pd l1 |
| topic | CTLA-4 PD-L1 PD-1 Immune checkpoint inhibitor therapies Immunotherapies Biomarkers |
| url | http://link.springer.com/article/10.1186/s41231-019-0032-9 |
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