Page 140 - Read Online

Page 8 Spiliopoulou et al. Cancer Drug Resist 2024;7:2 https://dx.doi.org/10.20517/cdr.2023.46

Table 2. Phenotype characteristics of T cells based on tissue distribution highlights the plasticity of T cells
reg
reg
Tissue T cell phenotype and function
reg
Brain IL-10, IL-33, IL-35, ST2, CTLA-4, TGF-β, IDO, 5-HT , AREG
7
Lung COX-2, PGE , TGF-β, AREG, IL-33, CD103, PHD, HIFα
2
Liver IL-10, IL-35, CTLA-4, TGF-β, SCFAs, AREG, RA, IDO1, COX2, PGE2, GITR, LAG3, ICOS, CD39/CD73, ST2
Adrenal gland β1-adrenergic receptors, Glucocorticoid receptor α
Lymph node IDO, TGF-β, CTLA-4, ICOS, CXCR5, IL-2, CD28, CD103
+
Skin IL-10, TGF-β, GITR, CTLA-4, Jag1, IDO, OX40 , ARG2, CCR4, CCR6, CLA
Bone CD39/CD73, RANK, PGE3, TGF-β, IDO, HIF1α, CXCR4
T cells: T regulatory cells; IL: interleukin; CTLA-4: cytotoxic T lymphocyte antigen-4; TGF-β: transforming growth factor beta; IDO: indoleamine-
reg
pyrrole 2,3-dioxygenase; AREG: amphiregulin; GITR: glucocorticoid-induced TNFR-related protein; LAG3: lymphocyte-activation gene 3; CCR: C-C
chemokine receptor.

(FC) was historically used to evaluate the T cells and their subsets [70,71] . Even today, the main advantage of
reg
flow cytometry is the quick turn-around time (i.e., generally within hours), and thus can be used to monitor
T cells before and after novel treatments. An alternative tool to monitor T cells is mass cytometry [72,73] .
reg
reg
Mass cytometry has a reduced risk of signal spill-over, thus improving background noise, and is a highly
dimensional method to assess several complex markers simultaneously. The disadvantage of mass
cytometry lies in the longer turn-around time, destruction of the specimen at the end of the examination,
and the subsequent bioinformatic analyses of high-volume data . The power of mass cytometry to measure
[74]
small subsets of immune cells in blood is exemplified in an ongoing clinical study with the
phosphoinositide-3-kinase delta (PI3K-δ) inhibitor roginolisib (IOA-244). In this study, mass cytometry
detected a reduction in blood T cells across dose cohorts, which was only marginally detected with
reg
[75]
standard FC .
In tumor specimens, standard immunohistochemistry has also provided early insights into changes in
T cells before and after treatment with standard or novel therapies [76-78] . Multiplex immunohistochemistry
reg
using a wide range of fluorochromes has increased the ability to simultaneously assess T cells and their
reg
interaction with adjacent cells, such as CD8 T cells . Like standard immunohistochemistry, multiplex
[79]
+
studies retain the anatomical features of the specimen and the spatial relationship of cells and stroma, for
example, the interaction of T cells with APC, CD8 T cells, or tumor cells .
+
[80]
reg
Transcriptomics provides another high-dimensional approach to assess T cells along with other changes
reg
in the tumor or blood . Gene expression profiles can describe the T cells along with other immune cells
[81]
reg
[82]
using whole tissue extracts . Under such conditions, the anatomical structure is lost for the benefit of
detecting low signal events. A modification of this technique is single-cell transcriptomics approaches,
which have revealed new functions of T cells . Using this technology, the destruction of the tumor
[83]
reg
specimen is kept to a minimum while the detection of cellular events is increased. The disadvantage of this
technology primarily lies in the processing and evaluation of high-volume data, which leads to long turn-
around times.
Like Transcriptomics, Proteomics is a collection of high-dimensional data of proteins either within tumor
tissue or proteins shed from tumors to the blood [84,85] . Thus, a wide range of secreted proteins can be
evaluated, including chemokines (e.g., CCL22) or cytokines (e.g., IL-2, TGF-β) associated with T cells .
[86]
reg
For drug development, Proteomics offers a broad discovery tool to study the effect of novel agents. From
this discovery platform, specific diagnostic tools can also be developed, such as companion diagnostics or
laboratory developed tests.