Inhibitory Receptors and Immune Checkpoints Regulating Natural Killer Cell Responses to Cancer

Buckle, Irina; Guillerey, Camille

doi:10.3390/cancers13174263

Cited by 38 publications

(33 citation statements)

References 204 publications

(309 reference statements)

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“…Immune checkpoint proteins play crucial roles in determining the ability of human cancer cells to escape immune surveillance ( 1 , 2 ). These proteins integrate into a complex machinery which is capable of blocking cytotoxic immune attacks on cancer cells by specialized human lymphoid cells and, in the long run, to fully suppress anti-tumor immunity ( 1 , 2 ).…”

Section: Introductionmentioning

confidence: 99%

Expression of the Immune Checkpoint Protein VISTA Is Differentially Regulated by the TGF-β1 – Smad3 Signaling Pathway in Rapidly Proliferating Human Cells and T Lymphocytes

et al. 2022

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Immune checkpoint proteins play crucial roles in human embryonic development but are also used by cancer cells to escape immune surveillance. These proteins and biochemical pathways associated with them form a complex machinery capable of blocking the ability of cytotoxic immune lymphoid cells to attack cancer cells and, ultimately, to fully suppress anti-tumor immunity. One of the more recently discovered immune checkpoint proteins is V-domain Ig-containing suppressor of T cell activation (VISTA), which plays a crucial role in anti-cancer immune evasion pathways. The biochemical mechanisms underlying regulation of VISTA expression remain unknown. Here, we report for the first time that VISTA expression is controlled by the transforming growth factor beta type 1 (TGF-β)-Smad3 signaling pathway. However, in T lymphocytes, we found that VISTA expression was differentially regulated by TGF-β depending on their immune profile. Taken together, our results demonstrate the differential biochemical control of VISTA expression in human T cells and various types of rapidly proliferating cells, including cancer cells, fetal cells and keratinocytes.

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Section: Introductionmentioning

confidence: 99%

Expression of the Immune Checkpoint Protein VISTA Is Differentially Regulated by the TGF-β1 – Smad3 Signaling Pathway in Rapidly Proliferating Human Cells and T Lymphocytes

et al. 2022

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“…This phase I/II trial uses CAR-NK cells specific for MUC-1 antigen expressed by different cancers, including NSCLC. Because activated NK cells, similarly to T cells, can express immune checkpoint molecules (e.g., PD-1, LAG-3, and TIM-3) that might inhibit NK anti-tumor responses their blockade with ICI could be envisaged in order to reinvigorate cytotoxic activity (138)(139)(140).…”

Section: Immunobiology Of Lung Cancermentioning

confidence: 99%

Therapeutic Implications of Tumor Microenvironment in Lung Cancer: Focus on Immune Checkpoint Blockade

et al. 2022

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In the last decade, the treatment of non-small cell lung cancer (NSCLC) has been revolutionized by the introduction of immune checkpoint inhibitors (ICI) directed against programmed death protein 1 (PD-1) and its ligand (PD-L1), or cytotoxic T lymphocyte antigen 4 (CTLA-4). In spite of these improvements, some patients do not achieve any benefit from ICI, and inevitably develop resistance to therapy over time. Tumor microenvironment (TME) might influence response to immunotherapy due to its prominent role in the multiple interactions between neoplastic cells and the immune system. Studies investigating lung cancer from the perspective of TME pointed out a complex scenario where tumor angiogenesis, soluble factors, immune suppressive/regulatory elements and cells composing TME itself participate to tumor growth. In this review, we point out the current state of knowledge involving the relationship between tumor cells and the components of TME in NSCLC as well as their interactions with immunotherapy providing an update on novel predictors of benefit from currently employed ICI or new therapeutic targets of investigational agents. In first place, increasing evidence suggests that TME might represent a promising biomarker of sensitivity to ICI, based on the presence of immune-modulating cells, such as Treg, myeloid derived suppressor cells, and tumor associated macrophages, which are known to induce an immunosuppressive environment, poorly responsive to ICI. Consequently, multiple clinical studies have been designed to influence TME towards a pro-immunogenic state and subsequently improve the activity of ICI. Currently, the mostly employed approach relies on the association of “classic” ICI targeting PD-1/PD-L1 and novel agents directed on molecules, such as LAG-3 and TIM-3. To date, some trials have already shown promising results, while a multitude of prospective studies are ongoing, and their results might significantly influence the future approach to cancer immunotherapy.

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“…Further NK cell co-inhibitory immune checkpoints also expressed by other immune cell types that are currently in the focus of interest are T cell immunoglobulin and mucin domain molecule 3 (Tim-3) [ 95 ], T cell immune receptor with immunoglobulin and ITIM domains (TIGIT) [ 96 ], and CD112 receptor (CD112R) [ 97 ]. Whereas Tim-3 recognizes galectin-9, HMGB1 and CEACAM1, the latter two are specific for the nectin family molecules CD112, CD113, and CD155 [ 98 ], as well as for the recently detected nectin-4 in the case of TIGIT only [ 96 ]. Nectins are frequently up-regulated on cancer cells.…”

Section: Harnessing Of Autologous Nk Cellsmentioning

confidence: 99%

“…Nectins are frequently up-regulated on cancer cells. They are also the ligands for the AR DNAM-1 (CD226) [ 98 ].…”

Section: Harnessing Of Autologous Nk Cellsmentioning

confidence: 99%

A Hot Topic: Cancer Immunotherapy and Natural Killer Cells

Michel

Ollert

Zimmer

2022

IJMS

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Despite significant progress in recent years, the therapeutic approach of the multiple different forms of human cancer often remains a challenge. Besides the well-established cancer surgery, radiotherapy and chemotherapy, immunotherapeutic strategies gain more and more attention, and some of them have already been successfully introduced into the clinic. Among these, immunotherapy based on natural killer (NK) cells is considered as one of the most promising options. In the present review, we will expose the different possibilities NK cells offer in this context, compare data about the theoretical background and mechanism(s) of action, report some results of clinical trials and identify several very recent trends. The pharmaceutical industry is quite interested in NK cell immunotherapy, which will benefit the speed of progress in the field.

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Inhibitory Receptors and Immune Checkpoints Regulating Natural Killer Cell Responses to Cancer

Cited by 38 publications

References 204 publications

Expression of the Immune Checkpoint Protein VISTA Is Differentially Regulated by the TGF-β1 – Smad3 Signaling Pathway in Rapidly Proliferating Human Cells and T Lymphocytes

Expression of the Immune Checkpoint Protein VISTA Is Differentially Regulated by the TGF-β1 – Smad3 Signaling Pathway in Rapidly Proliferating Human Cells and T Lymphocytes

Therapeutic Implications of Tumor Microenvironment in Lung Cancer: Focus on Immune Checkpoint Blockade

A Hot Topic: Cancer Immunotherapy and Natural Killer Cells

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