TY - JOUR
T1 - Bioinformatics approaches to profile the tumor microenvironment for immunotherapeutic discovery
AU - Clancy, Trevor
AU - Dannenfelser, Ruth
AU - Troyanskaya, Olga G.
AU - Malmberg, Karl Johan
AU - Hovig, Eivind
AU - Kristensen, Vessela
N1 - Publisher Copyright:
© 2017 Bentham Science Publishers.
PY - 2017/9/1
Y1 - 2017/9/1
N2 - In the microenvironment of a malignancy, tumor cells do not exist in isolation, but rather in a diverse ecosystem consisting not only of heterogeneous tumor-cell clones, but also normal cell types such as fibroblasts, vasculature, and an extensive pool of immune cells at numerous possible stages of activation and differentiation. This results in a complex interplay of diverse cellular signaling systems, where the immune cell component is now established to influence cancer progression and therapeutic response. It is experimentally difficult and laborious to comprehensively and systematically profile these distinct cell types from heterogeneous tumor samples in order to capitalize on potential therapeutic and biomarker discoveries. One emerging solution to address this challenge is to computationally extract cell-type specific information directly from bulk tumors. Such in silico approaches are advantageous because they can capture both the cell-type specific profiles and the tissue systems level of cell-cell interactions. Accurately and comprehensively predicting these patterns in tumors is an important challenge to overcome, not least given the success of immunotherapeutic drug treatment of several human cancers. This is especially challenging for subsets of closely related immune cell phenotypes with relatively small gene expression differences, which have critical functional distinctions. Here, we outline the existing and emerging novel bioinformatics strategies that can be used to profile the tumor immune landscape.
AB - In the microenvironment of a malignancy, tumor cells do not exist in isolation, but rather in a diverse ecosystem consisting not only of heterogeneous tumor-cell clones, but also normal cell types such as fibroblasts, vasculature, and an extensive pool of immune cells at numerous possible stages of activation and differentiation. This results in a complex interplay of diverse cellular signaling systems, where the immune cell component is now established to influence cancer progression and therapeutic response. It is experimentally difficult and laborious to comprehensively and systematically profile these distinct cell types from heterogeneous tumor samples in order to capitalize on potential therapeutic and biomarker discoveries. One emerging solution to address this challenge is to computationally extract cell-type specific information directly from bulk tumors. Such in silico approaches are advantageous because they can capture both the cell-type specific profiles and the tissue systems level of cell-cell interactions. Accurately and comprehensively predicting these patterns in tumors is an important challenge to overcome, not least given the success of immunotherapeutic drug treatment of several human cancers. This is especially challenging for subsets of closely related immune cell phenotypes with relatively small gene expression differences, which have critical functional distinctions. Here, we outline the existing and emerging novel bioinformatics strategies that can be used to profile the tumor immune landscape.
KW - Bioinformatics
KW - Gene expression profiling
KW - Immune-cell infiltration
KW - Immuno-oncology
KW - Immunotherapy
KW - Systems-immunology
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U2 - 10.2174/1381612823666170710154936
DO - 10.2174/1381612823666170710154936
M3 - Review article
C2 - 28699527
AN - SCOPUS:85044276926
SN - 1381-6128
VL - 23
SP - 4716
EP - 4725
JO - Current Pharmaceutical Design
JF - Current Pharmaceutical Design
IS - 32
ER -