Abstract
Functional systemic and local immunity is required for effective anti-tumor responses. In addition to an active engagement with cancer cells and tumor stroma, immune cells can be affected and are often found to be dysregulated in cancer patients. The impact of tumors on local and systemic immunity can be assessed using a variety of approaches ranging from low-dimensional analyses that are performed on large patient cohorts to multi-dimensional assays that are technically and logistically challenging and are therefore confined to a limited sample size. Many of these strategies have been established in recent years leading to exciting findings. Not only were analyses of immune cells in tumor patients able to predict the clinical course of the disease and patients’ survival, numerous studies also detected changes in the immune landscape that correlated with responses to novel immunotherapies. This review will provide an overview of established and novel tools for assessing immune cells in tumor patients and will discuss exemplary studies that utilized these techniques to predict patient outcomes.
Highlights
Described as “wounds that never heal” [1], tumors are intimately associated with inflammation and immune cells that can both promote and suppress cancer growth
Multi-parametric analysis on single cell level and comparison to resting and activated peripheral blood T cells allowed differentiation of CD8+ tumor-infiltrating lymphocyte (TIL) into 3 groups and revealed that the most enriched CD8+ TIL group highly expressed PD-1 while exhibiting an effector memory like phenotype [2] that has previously been linked to poor survival of renal cell carcinoma (RCC) patients [58]
An extensive mass cytometry-based analysis of RCC TIL has been performed by Chevrier et al This study broadly described the innate and adaptive immune landscape of RCC TIL and allowed outcome prediction based on patient allocation to one of specific clusters that have been defined by the co-expression of the pre-defined immune parameters [81]
Summary
Described as “wounds that never heal” [1], tumors are intimately associated with inflammation and immune cells that can both promote and suppress cancer growth. Several investigators correlated changes in peripheral blood immune populations with prognosis of cancer patients. Solid data are available showing a predictive potential of the neutrophil-to-lymphocyte ratio in several tumor entities [5,9,10,11] It is unknown if changes in the neutrophil/lymphocyte cell compartments reflect a specific tumor biology and the biological and translational relevance of these observations remains unclear. Human CD4+ T cells express FOXP3 upon activation and FOXP3 expression may not be sufficient to link a Treg phenotype to a suppressive function This phenomenon may play a role in the prognostic relevance of peripheral blood Treg in cancer patients. While increased Treg correlate with decreased survival of patients with several tumor entities, they can be associated with improved prognosis. No meta-data are available addressing the prognostic role of peripheral blood Treg across multiple tumor types, investigators observed an association between. Investigators often verify res to in situ assessments vitroinresults in animal analyze models, link the observed in vitro features to in to situ and and analyze vitro and results in animal models, link the observed in vitro features inassessments situ assessments analyze moremore thanthan one one tumor entity [21,22,23,24,25,26]
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