Correlation of T Cell Immunoglobulin and ITIM Domain (TIGIT) and Programmed Death 1 (PD-1) with Clinicopathological Characteristics of Renal Cell Carcinoma May Indicate Potential Targets for Treatment

Xin, Hong; Zhang, Xu

doi:10.12659/msm.910388

Cited by 23 publications

(22 citation statements)

References 23 publications

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“…Dual blockade of TIGIT and PD-1 in melanoma patients synergistically increased the proliferation, degranulation, and cytokine secretion of tumor-infiltrating and tumor antigen-specific CD8 + T cells, demonstrating a potential for dual blockage (175). Hong et al suggested that both PD-1 and TIGIT may serve as potential targets for the treatment of RCC as well (176). In GBM patients, such dual blockade has also shown to enhance anti-cancer immunity as well as survival (177).…”

Section: Tigit and Cd96mentioning

confidence: 99%

NK Cell-Based Immune Checkpoint Inhibition

Arooj²,

2020

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Immunotherapy, with an increasing number of therapeutic dimensions, is becoming an important mode of treatment for cancer patients. The inhibition of immune checkpoints, which are the source of immune escape for various cancers, is one such immunotherapeutic dimension. It has mainly been aimed at T cells in the past, but NK cells are a newly emerging target. Simultaneously, the number of checkpoints identified has been increasing in recent times. In addition to the classical NK cell receptors KIRs, LIRs, and NKG2A, several other immune checkpoints have also been shown to cause dysfunction of NK cells in various cancers and chronic infections. These checkpoints include the revolutionized CTLA-4, PD-1, and recently identified B7-H3, as well as LAG-3, TIGIT & CD96, TIM-3, and the most recently acknowledged checkpoint-members of the Siglecs family (Siglec-7/9), CD200 and CD47. An interesting dimension of immune checkpoints is their candidacy for dual-checkpoint inhibition, resulting in therapeutic synergism. Furthermore, the combination of immune checkpoint inhibition with other NK cell cytotoxicity restoration strategies could also strengthen its efficacy as an antitumor therapy. Here, we have undertaken a comprehensive review of the literature to date regarding NK cell-based immune checkpoints.

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Section: Tigit and Cd96mentioning

confidence: 99%

NK Cell-Based Immune Checkpoint Inhibition

Arooj²,

2020

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“… 129 , 130 Importantly, upregulation of TIM-3 has been found in gastric cancer, lung cancer, renal cancer, head and neck cancer, melanoma, schwannoma, follicular B-cell non-Hodgkin lymphoma, cervical cancer, prostate cancer, colorectal cancer, urothelial bladder carcinoma, esophageal cancer, and in the peripheral blood of patients with ovarian cancer. 35 , 93 , 131 – 143 The co-expression of PD-1 and TIM-3 correlates with acute myelogenous leukemia progression, suggesting that TIM-3 has potential as a prognostic biomarker for various cancers.…”

Section: Checkpoint Receptors and Ligands In Nk Cell Dysfunctionmentioning

confidence: 99%

“… 4 , 231 – 233 In addition, highly dense activated human primary NK cells can kill colorectal carcinoma cells grown in 3D cultures independent of PD-L1 expression, suggesting that the use of allogeneic activated NK cells could be an effective treatment of this cancer. 38 , 77 , 93 , 234 – 236 Immune evasion via PD-1/PD-L1 in NK cells and monocytes/macrophages is prominent in Hodgkin’s lymphoma. 38 , 77 , 93 , 234 – 237 Also, one of the immune checkpoint molecules that have already been employed in specific preclinical tumor models is the establishment of efficacy in blocking TIGIT to modulate NK cell function and has resulted in improved clinical responses in patients with cancer.…”

Section: Nk Cell As a Promising Therapeutic Target For Cancermentioning

confidence: 99%

“… 38 , 77 , 93 , 234 – 236 Immune evasion via PD-1/PD-L1 in NK cells and monocytes/macrophages is prominent in Hodgkin’s lymphoma. 38 , 77 , 93 , 234 – 237 Also, one of the immune checkpoint molecules that have already been employed in specific preclinical tumor models is the establishment of efficacy in blocking TIGIT to modulate NK cell function and has resulted in improved clinical responses in patients with cancer. 7 , 94 , 95 …”

Section: Nk Cell As a Promising Therapeutic Target For Cancermentioning

confidence: 99%

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Immune checkpoint molecules in natural killer cells as potential targets for cancer immunotherapy

Cao

Wang

Jin

et al. 2020

Sig Transduct Target Ther

104

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Recent studies have demonstrated the potential of natural killer (NK) cells in immunotherapy to treat multiple types of cancer. NK cells are innate lymphoid cells that play essential roles in tumor surveillance and control that efficiently kill the tumor and do not require the major histocompatibility complex. The discovery of the NK’s potential as a promising therapeutic target for cancer is a relief to oncologists as they face the challenge of increased chemo-resistant cancers. NK cells show great potential against solid and hematologic tumors and have progressively shown promise as a therapeutic target for cancer immunotherapy. The effector role of these cells is reliant on the balance of inhibitory and activating signals. Understanding the role of various immune checkpoint molecules in the exhaustion and impairment of NK cells when their inhibitory receptors are excessively expressed is particularly important in cancer immunotherapy studies and clinical implementation. Emerging immune checkpoint receptors and molecules have been found to mediate NK cell dysfunction in the tumor microenvironment; this has brought up the need to explore further additional NK cell-related immune checkpoints that may be exploited to enhance the immune response to refractory cancers. Accordingly, this review will focus on the recent findings concerning the roles of immune checkpoint molecules and receptors in the regulation of NK cell function, as well as their potential application in tumor immunotherapy.

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“…Research. The expression of TIGIT on tumor-infiltrating lymphocytes (TILs) has been reported via immunohistochemistry, western blotting, and PCR on hepatocellular carcinoma (HCC) (16), follicular lymphoma (FL) (17), squamous cell cancers (SCC)(5), Hodgkin's lymphoma (HL) (18), renal cell carcinoma (RCC) (19), small cell lung cancer (SCLC) (20), and melanoma (21). TIGIT has been validated as a therapeutic target, and anti-TIGIT therapies are currently being evaluated in in multiple clinical trials (Supplementary Table 1).…”

Section: Introductionmentioning

confidence: 99%

PET Imaging of TIGIT Expression on Tumor-Infiltrating Lymphocytes

Shaffer

Natarajan

Gambhir

2021

Clinical Cancer Research

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Purpose: Therapeutic checkpoint inhibitors on tumor-infiltrating lymphocytes (TIL) are being increasingly utilized in the clinic. The T-cell immunoreceptor with Ig and ITIM domains (TIGIT) is an inhibitory receptor expressed on T and natural killer cells. The TIGIT signaling pathway is an alternative target for checkpoint blockade to current PD-1/CTLA-4 strategies. Elevated TIGIT expression in the tumor microenvironment correlates with better therapeutic responses to anti-TIGIT therapies in preclinical models. Therefore, quantifying TIGIT expression in tumors is necessary for determining whether a patient may respond to anti-TIGIT therapy. PET imaging of TIGIT expression on TILs can therefore aid diagnosis and in monitoring therapeutic responses. Experimental Design: Antibody-based TIGIT imaging radiotracers were developed with the PET radionuclides copper-64 (64Cu) and zirconium-89 (89Zr). In vitro characterization of the imaging probes was followed by in vivo evaluation in both xenografts and syngeneic tumor models in mouse. Results: Two anti-TIGIT probes were developed and exhibited immunoreactivity of >72%, serum stability of >95%, and specificity for TIGIT with both mouse TIGIT-expressing HeLa cells and ex vivo–activated primary splenocytes. In vivo, the 89Zr-labeled probe demonstrated superior contrast than the 64Cu probe due to 89Zr's longer half-life matching the TIGIT antibody's pharmacokinetics. The 89Zr probe was used to quantify TIGIT expression on TILs in B16 melanoma in immunocompetent mice and confirmed by ex vivo flow cytometry. Conclusions: This study develops and validates novel TIGIT-specific 64Cu and 89Zr PET probes for quantifying TIGIT expression on TILs for diagnosis of patient selection for anti-TIGIT therapies.

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Correlation of T Cell Immunoglobulin and ITIM Domain (TIGIT) and Programmed Death 1 (PD-1) with Clinicopathological Characteristics of Renal Cell Carcinoma May Indicate Potential Targets for Treatment

Cited by 23 publications

References 23 publications

NK Cell-Based Immune Checkpoint Inhibition

NK Cell-Based Immune Checkpoint Inhibition

Immune checkpoint molecules in natural killer cells as potential targets for cancer immunotherapy

PET Imaging of TIGIT Expression on Tumor-Infiltrating Lymphocytes

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