Categorisation of patients based on immune profiles: a new approach to identifying candidates for response to checkpoint inhibitors
Abstract Objectives Inhibitors to the checkpoint proteins cytotoxic T‐lymphocyte‐associated protein 4 (CTLA‐4) and programmed cell death protein 1 (PD‐1) are becoming widely used in cancer treatment. However, a lack of understanding of the patient response to treatment limits accurate identification...
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doaj-a9d7365d75b84bc1aac430cf1734211c2021-04-29T11:54:30ZengWileyClinical & Translational Immunology2050-00682021-01-01104n/an/a10.1002/cti2.1267Categorisation of patients based on immune profiles: a new approach to identifying candidates for response to checkpoint inhibitorsSvetlana Bornschlegl0Michael P Gustafson1Danae A Delivanis2Mabel Ryder3Minetta C Liu4George Vasmatzis5Chris L Hallemeier6Sean S Park7Lewis R Roberts8Ian F Parney9Diane F Jelinek10Allan B Dietz11Immune Progenitor and Cell Therapy (IMPACT) Division of Experimental Pathology Mayo Clinic Rochester MN USAImmune Progenitor and Cell Therapy (IMPACT) Division of Experimental Pathology Mayo Clinic Rochester MN USADivision of Endocrinology, Diabetes, Metabolism, and Nutrition Mayo Clinic Rochester MN USADivision of Endocrinology, Diabetes, Metabolism, and Nutrition Mayo Clinic Rochester MN USADivision of Medical Oncology Mayo Clinic Rochester MN USADepartment of Molecular Medicine Mayo Clinic Rochester MN USADepartment of Radiation Oncology Mayo Clinic Rochester MN USADepartment of Radiation Oncology Mayo Clinic Rochester MN USADivision of Gastroenterology and Hepatology Mayo Clinic Rochester MN USADepartment of Neurosurgery Mayo Clinic Rochester MN USADepartment of Immunology Mayo Clinic Scottsdale AZ USAImmune Progenitor and Cell Therapy (IMPACT) Division of Experimental Pathology Mayo Clinic Rochester MN USAAbstract Objectives Inhibitors to the checkpoint proteins cytotoxic T‐lymphocyte‐associated protein 4 (CTLA‐4) and programmed cell death protein 1 (PD‐1) are becoming widely used in cancer treatment. However, a lack of understanding of the patient response to treatment limits accurate identification of potential responders to immunotherapy. Methods In this study, we assessed the expression of PD‐1 and CTLA‐4 on 19 leucocyte populations in the peripheral blood of 74 cancer patients. A reference data set for PD‐1 and CTLA‐4 was established for 40 healthy volunteers to determine the normal expression patterns for these checkpoint proteins. Results Unsupervised hierarchical clustering found four immune profiles shared across the solid tumor types, while chronic lymphocytic leukaemia patients had an immune profile largely unique to them. Furthermore, we measured these leucocyte populations on an additional cohort of 16 cancer patients receiving the PD‐1 inhibitor pembrolizumab in order to identify differences between responders and non‐responders, as well as compared to healthy volunteers (n = 20). We observed that cancer patients had pre‐treatment PD‐1 and CTLA‐4 expression on their leucocyte populations at different levels compared to healthy volunteers and identified two leucocyte populations positive for CTLA‐4 that had not been previously described. We found higher levels of PD‐1+ CD3+ CD4− CD8− cells in patients with progressive disease and have identified it as a potential biomarker of response, as well as identifying other significant differences in phenotypes between responders and non‐responders. Conclusion These results are suggestive that categorisation of patients based on immune profiles may differentiate responders from non‐responders to immunotherapy for solid tumors.https://doi.org/10.1002/cti2.1267checkpoint inhibitorsCTLA‐4immune monitoringimmune profilePD‐1programmed death 1 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Svetlana Bornschlegl Michael P Gustafson Danae A Delivanis Mabel Ryder Minetta C Liu George Vasmatzis Chris L Hallemeier Sean S Park Lewis R Roberts Ian F Parney Diane F Jelinek Allan B Dietz |
spellingShingle |
Svetlana Bornschlegl Michael P Gustafson Danae A Delivanis Mabel Ryder Minetta C Liu George Vasmatzis Chris L Hallemeier Sean S Park Lewis R Roberts Ian F Parney Diane F Jelinek Allan B Dietz Categorisation of patients based on immune profiles: a new approach to identifying candidates for response to checkpoint inhibitors Clinical & Translational Immunology checkpoint inhibitors CTLA‐4 immune monitoring immune profile PD‐1 programmed death 1 |
author_facet |
Svetlana Bornschlegl Michael P Gustafson Danae A Delivanis Mabel Ryder Minetta C Liu George Vasmatzis Chris L Hallemeier Sean S Park Lewis R Roberts Ian F Parney Diane F Jelinek Allan B Dietz |
author_sort |
Svetlana Bornschlegl |
title |
Categorisation of patients based on immune profiles: a new approach to identifying candidates for response to checkpoint inhibitors |
title_short |
Categorisation of patients based on immune profiles: a new approach to identifying candidates for response to checkpoint inhibitors |
title_full |
Categorisation of patients based on immune profiles: a new approach to identifying candidates for response to checkpoint inhibitors |
title_fullStr |
Categorisation of patients based on immune profiles: a new approach to identifying candidates for response to checkpoint inhibitors |
title_full_unstemmed |
Categorisation of patients based on immune profiles: a new approach to identifying candidates for response to checkpoint inhibitors |
title_sort |
categorisation of patients based on immune profiles: a new approach to identifying candidates for response to checkpoint inhibitors |
publisher |
Wiley |
series |
Clinical & Translational Immunology |
issn |
2050-0068 |
publishDate |
2021-01-01 |
description |
Abstract Objectives Inhibitors to the checkpoint proteins cytotoxic T‐lymphocyte‐associated protein 4 (CTLA‐4) and programmed cell death protein 1 (PD‐1) are becoming widely used in cancer treatment. However, a lack of understanding of the patient response to treatment limits accurate identification of potential responders to immunotherapy. Methods In this study, we assessed the expression of PD‐1 and CTLA‐4 on 19 leucocyte populations in the peripheral blood of 74 cancer patients. A reference data set for PD‐1 and CTLA‐4 was established for 40 healthy volunteers to determine the normal expression patterns for these checkpoint proteins. Results Unsupervised hierarchical clustering found four immune profiles shared across the solid tumor types, while chronic lymphocytic leukaemia patients had an immune profile largely unique to them. Furthermore, we measured these leucocyte populations on an additional cohort of 16 cancer patients receiving the PD‐1 inhibitor pembrolizumab in order to identify differences between responders and non‐responders, as well as compared to healthy volunteers (n = 20). We observed that cancer patients had pre‐treatment PD‐1 and CTLA‐4 expression on their leucocyte populations at different levels compared to healthy volunteers and identified two leucocyte populations positive for CTLA‐4 that had not been previously described. We found higher levels of PD‐1+ CD3+ CD4− CD8− cells in patients with progressive disease and have identified it as a potential biomarker of response, as well as identifying other significant differences in phenotypes between responders and non‐responders. Conclusion These results are suggestive that categorisation of patients based on immune profiles may differentiate responders from non‐responders to immunotherapy for solid tumors. |
topic |
checkpoint inhibitors CTLA‐4 immune monitoring immune profile PD‐1 programmed death 1 |
url |
https://doi.org/10.1002/cti2.1267 |
work_keys_str_mv |
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