Mechanisms of Immunotoxicology in Cancer Patients
Summary
The purpose of this study is to better understand how the treatment of cancer with immune checkpoint inhibitors (ICI) leads to the development of autoimmunity. Specifically, we wish to understand the genetics and immune system features that cause a subset of cancer patients treated with checkpoint inhibitor therapy to develop an immune-related adverse event (irAE).
Detailed description
The goal of this study is to understand how the treatment of cancer with checkpoint inhibitors leads to the development of autoimmunity. Specifically, to understand the genetics and immune system features that cause a subset of cancer patients treated with checkpoint inhibitors to develop autoimmunity. At least 300 patients will be enrolled when they are initially prescribed any checkpoint inhibitor. Peripheral blood and serum from patients when they enroll and examine the genetics, serum factors, and phenotype of the immune system. There is no planned intervention. Subjects will be asked to provide peripheral blood and serum at established time points when they are getting therapeutic infusions and routine clinical labs, as well as, at the time they develop any autoimmune symptoms. Urine may also be collected at the time of enrollment, standard study visits, and/or at the time of an autoimmune complication. Inclusion criteria include a diagnosis of cancer, prescription for a checkpoint inhibitor, and fluency in English. Exclusion criteria include any subjects not willing or able to give consent, children under the age of 18, and history of transplant. There will not be any interventions. Clinical data will be extracted from electronic medical records. Coded data will be stored in a REDCap database. Protected health information (PHI) and study key stored at UPenn on a password-protected database on an encrypted drive that is institutionally secured and managed by the University of Pennsylvania.
Arms & interventions
Outcome measures
Primary
The phenotype and function of peripheral blood cells (i.e., CD4+ T cells, CD8+ T cells, B cells, myeloid cells) characteristic to patients receiving checkpoint inhibitor therapy.
The phenotypic analysis will include multiple surface markers that define populations of cells, including activated, memory, and regulatory populations. Cells will also be activated to determine which cytokines are produced.
Time frame: 6 years
The prevalence of immune-related adverse events (irAEs) that complicate checkpoint inhibitor therapy.
This is a pilot analysis to better understand how the treatment of cancer with immune checkpoint inhibitors leads to the development of autoimmunity in a subset of cancer patients.
Time frame: 6 years
Secondary
The number of future research studies and/or collaborations resulting directly from the databank of tissues and other relevant clinical information that will be established.
Time frame: 6 years
Eligibility criteria
Study locations (1)
University of Pennsylvania - Abramson Cancer Center
Philadelphia, Pennsylvania, 19104