Abstract
The success of immunotherapy that targets inhibitory T cell receptors for the treatment of multiple cancers has seen the anti-tumor immune response re-emerge as a promising biomarker of response to therapy. Longitudinal characterization of T cells in the tumor microenvironment (TME) helps us understand how to promote effective anti-tumor immunity. However, serial analyses at the tumor site are rarely feasible in clinical practice. Malignant pleural effusions (MPE) associated with thoracic cancers are an abnormal accumulation of fluid in the pleural space that is routinely drained for patient symptom control. This fluid contains tumor cells and immune cells, including lymphocytes, macrophages and dendritic cells, providing a window into the local tumor microenvironment. Recurrent MPE is common, and provides an opportunity for longitudinal analysis of the tumor site in a clinical setting. Here, we review the phenotype of MPE-derived T cells, comparing them to tumor and blood T cells. We discuss the benefits and limitations of their use as potential dynamic biomarkers of response to therapy.
Highlights
Specialty section: This article was submitted to Cancer Immunity and Immunotherapy, a section of the journal Frontiers in Oncology
Malignant pleural effusions (MPE) associated with thoracic cancers are an abnormal accumulation of fluid in the pleural space that is routinely drained for patient symptom control
We review changes in T cells derived from MPEs of patients undergoing Immune checkpoint blockade (ICB), and whether these changes were associated with treatment outcomes
Summary
A malignant pleural effusion (MPE) is an abnormal accumulation of fluid in the pleural space associated with advanced stage disease and poor clinical outcomes [1, 2]. Platinum-based chemotherapies may synergize with ICB, with single arm studies showing that combination chemo-immunotherapy reduces tumor burden and shows promising progression-free and overall survival outcomes for mesothelioma [17,18,19]. ICB is expensive and can cause severe immune-related toxicities, highlighting the need to develop biomarkers that can accurately predict patient outcomes and inform clinical decisions [27]. We discuss the unique opportunities and challenges a longitudinal study of MPE T cells brings, in terms of improving our understanding of therapeutic mechanisms, and developing a biomarker of response to ICB
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