Dataset Information

PSGL-1 Immune Checkpoint Inhibition for CD4⁺ T Cell Cancer Immunotherapy.

ABSTRACT: Immune checkpoint inhibition targeting T cells has shown tremendous promise in the treatment of many cancer types and are now standard therapies for patients. While standard therapies have focused on PD-1 and CTLA-4 blockade, additional immune checkpoints have shown promise in promoting anti-tumor immunity. PSGL-1, primarily known for its role in cellular migration, has also been shown to function as a negative regulator of CD4⁺ T cells in numerous disease settings including cancer. PSGL-1 is highly expressed on T cells and can engage numerous ligands that impact signaling pathways, which may modulate CD4⁺ T cell differentiation and function. PSGL-1 engagement in the tumor microenvironment may promote CD4⁺ T cell exhaustion pathways that favor tumor growth. Here we highlight that blocking the PSGL-1 pathway on CD4⁺ T cells may represent a new cancer therapy approach to eradicate tumors.

SUBMITTER: DeRogatis JM

PROVIDER: S-EPMC7940186 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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Publications

PSGL-1 Immune Checkpoint Inhibition for CD4<sup>+</sup> T Cell Cancer Immunotherapy.

DeRogatis Julia M JM Viramontes Karla M KM Neubert Emily N EN Tinoco Roberto R

Frontiers in immunology 20210223

Immune checkpoint inhibition targeting T cells has shown tremendous promise in the treatment of many cancer types and are now standard therapies for patients. While standard therapies have focused on PD-1 and CTLA-4 blockade, additional immune checkpoints have shown promise in promoting anti-tumor immunity. PSGL-1, primarily known for its role in cellular migration, has also been shown to function as a negative regulator of CD4<sup>+</sup> T cells in numerous disease settings including cancer. P ...[more]

PMID: 33708224

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Project description:Malignant cells have the capacity to rapidly grow exponentially and spread in part by suppressing, evading, and exploiting the host immune system. Immunotherapy is a form of oncologic treatment directed towards enhancing the host immune system against cancer. In recent years, manipulation of immune checkpoints or pathways has emerged as an important and effective form of immunotherapy. Agents that target cytotoxic T lymphocyte-associated molecule-4 (CTLA-4), programmed cell death receptor-1 (PD-1), and programmed cell death ligand-1 (PD-L1) are the most widely studied and recognized. Immunotherapy, however, extends beyond immune checkpoint therapy by using new molecules such as chimeric monoclonal antibodies and antibody drug conjugates that target malignant cells and promote their destruction. Genetically modified T cells expressing chimeric antigen receptors are able to recognize specific antigens on cancer cells and subsequently activate the immune system. Native or genetically modified viruses with oncolytic activity are of great interest as, besides destroying malignant cells, they can increase anti-tumor activity in response to the release of new antigens and danger signals as a result of infection and tumor cell lysis. Vaccines are also being explored, either in the form of autologous or allogenic tumor peptide antigens, genetically modified dendritic cells that express tumor peptides, or even in the use of RNA, DNA, bacteria, or virus as vectors of specific tumor markers. Most of these agents are yet under development, but they promise to be important options to boost the host immune system to control and eliminate malignancy. In this review, we have provided detailed discussion of different forms of immunotherapy agents other than checkpoint-modifying drugs. The specific focus of this manuscript is to include first-in-human phase I and phase I/II clinical trials intended to allow the identification of those drugs that most likely will continue to develop and possibly join the immunotherapeutic arsenal in a near future.

Project description:The interaction of the host immune system with tumor cells in the tissue microenvironment is essential in understanding tumor immunity and development of successful cancer immunotherapy. The presence of lymphocytes in tumors is highly correlated with an improved outcome. T cells have a set of cell surface receptors termed immune checkpoints that when activated suppress T cell function. Upregulation of immune checkpoint receptors such as programmed cell death 1 (PD-1) and cytotoxic T lymphocyte associated protein 4 (CTLA-4) occurs during T cell activation in an effort to prevent damage from an excessive immune response. Immune checkpoint inhibitors allow the adaptive immune system to respond to tumors more effectively. There has been clinical success in different types of cancer blocking immune checkpoint receptors such as PD-1 and CTLA. However, relapse has occurred. The innate and acquired/therapy induced resistance to treatment has been encountered. Aberrant cellular signal transduction is a major contributing factor to resistance to immunotherapy. Combination therapies with other co-inhibitory immune checkpoints such as TIM-3, LAG3 and VISTA are currently being tested to overcome resistance to cancer immunotherapy. Expression of TIM-3 has been associated with resistance to PD-1 blockade and combined blockade of TIM-3 and PD-1 has demonstrated improved responses in preclinical models. LAG3 blockade has the potential to increase the responsiveness of cytotoxic T-cells to tumors. Furthermore, tumors that were found to express VISTA had an increased rate of growth due to the T cell suppression. The growing understanding of the inhibitory immune checkpoints' ligand biology, signaling mechanisms, and T-cell suppression in the tumor microenvironment continues to fuel preclinical and clinical advancements in design, testing, and approval of agents that block checkpoint molecules. Our review seeks to bridge fundamental regulatory mechanisms across inhibitory immune checkpoint receptors that are of great importance in resistance to cancer immunotherapy. We will summarize the biology of different checkpoint molecules, highlight the effect of individual checkpoint inhibition as anti-tumor therapies, and outline the literatures that explore mechanisms of resistance to individual checkpoint inhibition pathways.

Dataset Information

PSGL-1 Immune Checkpoint Inhibition for CD4⁺ T Cell Cancer Immunotherapy.

Publications

PSGL-1 Immune Checkpoint Inhibition for CD4<sup>+</sup> T Cell Cancer Immunotherapy.

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Dataset Information

PSGL-1 Immune Checkpoint Inhibition for CD4+ T Cell Cancer Immunotherapy.

Publications

PSGL-1 Immune Checkpoint Inhibition for CD4<sup>+</sup> T Cell Cancer Immunotherapy.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

PSGL-1 Immune Checkpoint Inhibition for CD4⁺ T Cell Cancer Immunotherapy.