Soluble B7-CD28 Family Inhibitory Immune Checkpoint Proteins and Anti-Cancer Immunotherapy

Khan, Muhammad Saleem Iqbal; Arooj, Sumbal; Wang, Hua

doi:10.3389/fimmu.2021.651634

Cited by 58 publications

(49 citation statements)

References 255 publications

(736 reference statements)

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“…Furthermore, soluble B7-CD28 family inhibitory immune checkpoint proteins (including soluble CTLA-4, soluble B7-1 and soluble B7-H4) play a wide role in anti-cancer immunomodulatory regulation. Therefore, these may serve as valuable prognostic biomarkers that can predict the therapeutic response, while also opening up new opportunities for anticancer immunotherapy ( 67 ).…”

Section: Biomarkers Of Ici Therapeutic Efficacy Against Digestive Sys...mentioning

confidence: 99%

Research Progress of Biomarkers for Immune Checkpoint Inhibitors on Digestive System Cancers

Wang

et al. 2022

Front. Immunol.

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Immunotherapy represented by immune checkpoint inhibitors has gradually entered a new era of precision medicine. In view of the limited clinical benefits of immunotherapy in patients with digestive system cancers, as well as the side-effects and high treatment costs, development of biomarkers to predict the efficacy of immune therapy is a key imperative. In this article, we review the available evidence of the value of microsatellite mismatch repair, tumor mutation burden, specific mutated genes or pathways, PD-L1 expression, immune-related adverse reactions, blood biomarkers, and patient-related biomarkers in predicting the efficacy of immunotherapy against digestive system cancers. Establishment of dynamic personalized prediction models based on multiple biomarkers is a promising area for future research.

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Section: Biomarkers Of Ici Therapeutic Efficacy Against Digestive Sys...mentioning

confidence: 99%

Research Progress of Biomarkers for Immune Checkpoint Inhibitors on Digestive System Cancers

Wang

et al. 2022

Front. Immunol.

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“…The limited clinical success of ICI therapy may be explained in part both by its detrimental effects on non-intended target cell populations, as discussed in this review, and the compensatory upregulation of non-targeted ICs [ 414 ]. Moreover, any ICs and many of the corresponding ligands have been shown to be apparent also in a soluble form in serum, generated either by proteolytic cleavage of alternative gene splicing [ 415 ]. Soluble ICs serve as biomarkers and prognostic factors, e.g., in tumor patients, are dynamically regulated, e.g., in response to tumor therapy, and exert biological functions [ 416 ].…”

Section: Conclusion/perspectivesmentioning

confidence: 99%

Immunomodulatory Properties of Immune Checkpoint Inhibitors—More than Boosting T-Cell Responses?

Kuske

Haist

Jung

et al. 2022

Cancers

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The approval of immune checkpoint inhibitors (ICI) that serve to enhance effector T-cell anti-tumor responses has strongly improved success rates in the treatment of metastatic melanoma and other tumor types. The currently approved ICI constitute monoclonal antibodies blocking cytotoxic T-lymphocyte-associated protein (CTLA)-4 and anti-programmed cell death (PD)-1. By this, the T-cell-inhibitory CTLA-4/CD80/86 and PD-1/PD-1L/2L signaling axes are inhibited. This leads to sustained effector T-cell activity and circumvents the immune evasion of tumor cells, which frequently upregulate PD-L1 expression and modulate immune checkpoint molecule expression on leukocytes. As a result, profound clinical responses are observed in 40–60% of metastatic melanoma patients. Despite the pivotal role of T effector cells for triggering anti-tumor immunity, mounting evidence indicates that ICI efficacy may also be attributable to other cell types than T effector cells. In particular, emerging research has shown that ICI also impacts innate immune cells, such as myeloid cells, natural killer cells and innate lymphoid cells, which may amplify tumoricidal functions beyond triggering T effector cells, and thus improves clinical efficacy. Effects of ICI on non-T cells may additionally explain, in part, the character and extent of adverse effects associated with treatment. Deeper knowledge of these effects is required to further develop ICI treatment in terms of responsiveness of patients to treatment, to overcome resistance to ICI and to alleviate adverse effects. In this review we give an overview into the currently known immunomodulatory effects of ICI treatment in immune cell types other than the T cell compartment.

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“…In the capacity that SHP2 enhances T-cell activation, it has been shown to dephosphorylate inhibitory sites of positive regulators including AKT and ERK and activating sites of negative regulators including CSK, CRK, and PAG ( Frearson and Alexander, 1998 ; Chemnitz et al, 2004 ; Bardhan et al, 2019 ; Celis-Gutierrez et al, 2019 ). Downstream of PD-1, the main evidence of a contribution of SHP2 function comes from the dephosphorylation of the coreceptor CD28 ( Hui et al, 2017 ; Khan et al, 2021 ). Perhaps sublocalization and temporal segregation of signaling can best explain these dual, even opposing, roles for SHP2 ( Valitutti et al, 2010 ).…”

Section: Introductionmentioning

confidence: 99%

Bridging the Gap: Connecting the Mechanisms of Immune-Related Adverse Events and Autoimmunity Through PD-1

Mor

Strazza

2022

Front. Cell Dev. Biol.

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The emergence of anti–cytotoxic T-lymphocyte antigen 4 (anti-CTLA-4), anti–programmed cell death 1 ligand (anti–PD-1), and anti–PD-L1 antibodies as immune checkpoint inhibitors (ICIs) revolutionized the treatment of numerous types of tumors. These antibodies, both alone and in combination, provide great clinical efficacy as evidenced by tumor regression and increased overall patients’ survival. However, with this success comes multiple challenges. First, while patients who respond to ICIs have outstanding outcomes, there remains a large proportion of patients who do not respond at all. This all-or-none response has led to looking downstream of programmed cell death 1 (PD-1) for additional therapeutic targets and for new combination therapies. Second, a majority of patients who receive ICIs go on to develop immune-related adverse events (irAEs) characterized by end-organ inflammation with T-cell infiltrates. The hallmarks of these clinically observed irAEs share many similarities with primary autoimmune diseases. The contribution of PD-1 to peripheral tolerance is a major mechanism for protection against expansion of self-reactive T-cell clones and autoimmune disease. In this review, we aim to bridge the gaps between our cellular and molecular knowledge of PD-1 signaling in T cells, ICI-induced irAEs, and autoimmune diseases. We will highlight shared mechanisms and the potential for new therapeutic strategies.

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Soluble B7-CD28 Family Inhibitory Immune Checkpoint Proteins and Anti-Cancer Immunotherapy

Cited by 58 publications

References 255 publications

Research Progress of Biomarkers for Immune Checkpoint Inhibitors on Digestive System Cancers

Research Progress of Biomarkers for Immune Checkpoint Inhibitors on Digestive System Cancers

Immunomodulatory Properties of Immune Checkpoint Inhibitors—More than Boosting T-Cell Responses?

Bridging the Gap: Connecting the Mechanisms of Immune-Related Adverse Events and Autoimmunity Through PD-1

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