Abstract
Immune checkpoints are intensively investigated as targets in cancer immunotherapy. T-cell immunoreceptor with immunoglobulin (Ig) and ITIM domains (TIGIT) are recently emerging as a novel promising target in cancer immunotherapy. Herein, we systematically investigated TIGIT-related transcriptome profile and relevant clinical information derived from a total of 2994 breast cancer patients recorded in The Cancer Genome Atlas (TCGA) and Molecular Taxonomy of Breast Cancer International Consortium (METABRIC). We uncovered the relationship between TIGIT and major molecular and clinical characteristics in breast cancer. More importantly, we depicted the landscape of associations between TIGIT and other immune cell populations. Gene ontology analyses and Gene Set Variation Analysis (GSVA) of genes correlated with TIGIT revealed that TIGIT were mainly involved in immune responses and inflammatory activities. In summary, TIGIT expression was tightly related to the aggressiveness of breast cancer; TIGIT might manipulate anti-tumor immune responses by impacting not only T cells but also other immune cells. To the best of our knowledge, this is by far the most comprehensive and largest study characterizing the molecular and clinical features of TIGIT in breast cancer through large-scale transcriptome data.
Highlights
Breast cancer is the most frequently diagnosed cancers and the leading cause of cancer-related deaths in females worldwide [1]
To further characterize the expression pattern of TIGIT in breast cancer, we examined the RNA-sequencing data of breast cancer from The Cancer Genome Atlas (TCGA) and METABRIC databases, the association of TIGIT and clinical characteristics are listed in Tables 1 and 2
TIGIT overexpression was observed in triple-negative breast cancer (TNBC) than none-TNBC samples (Figure 2C,D)
Summary
Breast cancer is the most frequently diagnosed cancers and the leading cause of cancer-related deaths in females worldwide [1]. Induction of an exhausted phenotype in effector lymphocytes and thereby preventing effective tumor rejection represents one of the mechanisms of immune escape [3]. Cancer immunotherapy by inhibiting these immune checkpoints to reactivate the cytotoxic phenotype are emerging as a novel promising treatment strategy for cancer. Due to remarkable survival benefits of cancer immunotherapy, FDA approved the treatment of several cancer entities by using antibodies blocking the negative immune checkpoint molecules, cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), programmed cell death protein 1 (PD-1) or PD-1 ligand 1 (PD-L1) [5]. A large proportion of cancer patients failed to respond to the treatment of blocking antibodies against the PD-1, PD-L1 or CTLA-4 immune checkpoint axis [6,7,8]. More endeavors are warranted to the therapeutic evaluation of additional immune checkpoints
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