Patterns of TIGIT Expression in Lymphatic Tissue, Inflammation, and Cancer

Blessin, Niclas C.; Simon, Ronald; Kluth, Martina; Fischer, Kristine; Hube‐Magg, Claudia; Li, Wenchao; Makrypidi‐Fraune, Georgia; Wellge, Björn; Mandelkow, Tim; Debatin, Nicolaus F.; Höflmayer, Doris; Lennartz, Maximilian; Sauter, Guido; Izbicki, Jakob R.; Minner, Sarah; Büscheck, Franziska; Uhlig, Ria; Dum, David; Krech, Till; Luebke, Andreas M.; Wittmer, Corinna; Jacobsen, Frank; Burandt, Eike-Christian; Steurer, Stefan; Wilczak, Waldemar; Hinsch, Andrea

doi:10.1155/2019/5160565

Cited by 54 publications

(40 citation statements)

References 53 publications

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“…TIGIT is highly expressed on NK cells, CD8 + T cells and Treg cells within the TME. [188][189][190][191] Its ligands CD155 and CD112 are widely expressed on tumor cells. [192][193][194] Multiple studies showed that TIGIT signaling is involved in dampening both T-cell activation and differentiation into anti-tumor effector cells.…”

Section: T-cell Exhaustion In Cancermentioning

confidence: 99%

The yin and yang of co-inhibitory receptors: toward anti-tumor immunity without autoimmunity

Schnell¹,

Bod²,

Madi³

et al. 2020

Cell Res

157

104

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Co-inhibitory receptors are important regulators of T-cell function that define the balance between tolerance and autoimmunity. The immune regulatory function of co-inhibitory receptors, including CTLA-4, PD-1, TIM-3, TIGIT, and LAG-3, was first discovered in the setting of autoimmune disease models, in which their blockade or deficiency resulted in induction or exacerbation of the disease. Later on, co-inhibitory receptors on lymphocytes have also been found to influence outcomes in tumor and chronic viral infection settings. These receptors suppress T-cell function in the tumor microenvironment (TME), thereby making the T cells dysfunctional. Based on this observation, blockade of co-inhibitory receptors (also known as checkpoint molecules) has emerged as a successful treatment option for a number of human cancers. However, severe autoimmune-like side effects limit the use of therapeutics that block individual or combinations of co-inhibitory receptors for cancer treatment. In this review we provide an overview of the role of co-inhibitory receptors in autoimmunity and anti-tumor immunity. We then discuss current approaches and future directions to leverage our knowledge of co-inhibitory receptors to target them in tumor immunity without inducing autoimmunity.

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Section: T-cell Exhaustion In Cancermentioning

confidence: 99%

The yin and yang of co-inhibitory receptors: toward anti-tumor immunity without autoimmunity

Schnell¹,

Bod²,

Madi³

et al. 2020

Cell Res

157

104

View full text Add to dashboard Cite

show abstract

“…Recently, interest in other immune checkpoints has intensified and novel potential targets have been identified such as TIM-3, LAG-3, TIGIT, or VISTA. Expressed on activated T cells and NK cells among others, these receptors have been found highly expressed on TILs as compared to circulating T cells in CRC patients (127)(128)(129)(130). As with PD-1 or CTLA-4, physiologically, these inhibitory receptors are induced following the activation of T cells to prevent overstimulation, which may result in an exhausted state.…”

Section: Future Alternatives: New Generation Of Immune Checkpoint Inhmentioning

confidence: 99%

Relationships Between Immune Landscapes, Genetic Subtypes and Responses to Immunotherapy in Colorectal Cancer

et al. 2020

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Colorectal cancer (CRC) is highly heterogeneous at the genetic and molecular level, which has major repercussions on the efficacy of immunotherapy. A small subset of CRCs exhibit microsatellite instability (MSI), a molecular indicator of defective DNA mismatch repair (MMR), but the majority are microsatellite-stable (MSS). The high tumor mutational burden (TMB) and neoantigen load in MSI tumors favors the infiltration of immune effector cells, and antitumor immune responses within these tumors are strong relative to their MSS counterparts. MSI has emerged as a major predictive marker for the efficacy of immune checkpoint blockade over the last few years and nivolumab or pembrolizumab targeting PD-1 has been approved for patients with MSI refractory or metastatic CRC. However, some MSS tumors show DNA polymerase epsilon (POLE) mutations that also confer a very high TMB and may also be heavily infiltrated by immune cells making them amenable to respond to immune checkpoint inhibitors (ICI). In this review we discuss the role of the different immune landscapes in CRC and their relationships with defined CRC genetic subtypes. We discuss potential reasons why immune checkpoint blockade has met with limited success for the majority of CRC patients, despite the finding that immune cell infiltration of primary non-metastatic tumors is a strong predictive, and prognostic factor for relapse and survival. We then consider in which ways CRC cells develop mechanisms to resist ICI. Finally, we address the latest advances in CRC vaccination and how a personalized neoantigen vaccine strategy might overcome the resistance of MSI and MSS tumors in patients for whom immune checkpoint blockade is not a treatment option.

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“…This was expected because in an earlier study using a comparable experimental set-up, we had also regularly found TIGIT expression in a considerable fraction of lymphocytic cells in healthy lymphatic organs, various inflammatory diseases and in samples of lung and colorectal cancers (19). Taken together, these findings strongly support the concept that TIGIT expression is an inherent feature of T cell lymphocytic infiltrations in normal, inflammatory and cancerous tissues (19). Earlier studies using flow cytometry have also described regular presence of TIGIT + T cells in these immune microenvironments (13,17,21,24,25).…”

Section: Discussionmentioning

confidence: 52%

“…T cell immunoreceptor with Ig and ITIM domain (TIGIT), a co-inhibitory transmembrane glycoprotein of the poliovirus receptor (PVR)/nectin superfamily, is another interesting candidate for novel checkpoint therapies (13,14). In mouse models and ongoing clinical studies, blockade or ablation of TIGIT, alone or in combination with blockade of PD-1, can restore tumor suppressive effects (15–19). These findings indicate that TIGIT, similar to PD-1, has a crucial role in inhibiting the tumor-directed immune response and, thus, might be a suitable and relevant target for novel immune-modulating therapies.…”

Section: Introductionmentioning

confidence: 99%

Expression of the immune checkpoint receptor TIGIT in seminoma

et al. 2019

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A characteristic feature of testicular seminoma is the abundance of immune cells in the tumor microenvironment, raising the possibility that immune checkpoint inhibitors may serve as a therapeutic option in these types of tumors. T cell immunoreceptor with Ig and ITIM domains (TIGIT) is an inhibitory immune checkpoint receptor in analogy to PD-1, and drugs targeting TIGIT are currently being investigated in clinical trials. Little is known about the expression of these proteins in testicular seminomas. Therefore the present study performed immunohistochemical analysis to determine the relative abundance of TIGIT and PD-1 in relation to the total CD3 + immune cell infiltration in a tissue microarray (TMA) constructed from 78 seminoma patients. The fraction of TIGIT + and PD-1 + lymphocytes was highly variable in individual cancers and ranged from 2.3 to 69.4% (mean: 32.2±14.7%) for TIGIT and from 0.8 to 56.5% (mean: 21.6±13.2%) for PD-1. The same high degree of variability was also identified for the ratio of PD-1 to TIGIT positive cells, which varied from a dominance of TIGIT (PD-1: TIGIT ratio=0.02) in 74% of patients, to a predominance of PD-1 (PD-1: TIGIT ratio=12.5) in 23% of patients. In summary, the immune checkpoint receptors TIGIT and PD-1 are abundantly expressed in human seminomas. Once available, anti-TIGIT antibodies, possibly in combination with anti-PD-1 drugs, may be a reasonable therapeutic strategy for this type of cancer.

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Patterns of TIGIT Expression in Lymphatic Tissue, Inflammation, and Cancer

Cited by 54 publications

References 53 publications

The yin and yang of co-inhibitory receptors: toward anti-tumor immunity without autoimmunity

The yin and yang of co-inhibitory receptors: toward anti-tumor immunity without autoimmunity

Relationships Between Immune Landscapes, Genetic Subtypes and Responses to Immunotherapy in Colorectal Cancer

Expression of the immune checkpoint receptor TIGIT in seminoma

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