Immune Checkpoint Inhibitors in Cancer Therapy

Shiravand, Yavar; Khodadadi, Faezeh; Kashani, Seyyed Mohammad Amin; Hosseini‐Fard, Seyed Reza; Hosseini, Shadi; Sadeghirad, Habib; Ladwa, Rahul; O’Byrne, K.J.; Kulasinghe, Arutha

doi:10.3390/curroncol29050247

Cited by 341 publications

(233 citation statements)

References 147 publications

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“…To date the ICIs approved by the FDA include blocking antibodies targeting cytotoxic T-lymphocyte protein 4 (CTLA-4) (ipilimumab) and programmed cell death protein 1 (PD-1) (pembrolizumab, nivolumab, cemiplimab, dostarlimab) and its ligand PD-L1 (atezolizumab, avelumab, durvalumab) [9]. However, several other antibody ICIs have been approved by other agencies eg the anti-PD-1 antibodies sintilimab, camrelizumab and zimberelimab [10] (https:// clini caltr ials.…”

Section: Immune Checkpoint Inhibitorsmentioning

confidence: 99%

Enhancing therapeutic anti-cancer responses by combining immune checkpoint and tyrosine kinase inhibition

et al. 2022

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Over the past decade, immune checkpoint inhibitor (ICI) therapy has been established as the standard of care for many types of cancer, but the strategies employed have continued to evolve. Recently, much clinical focus has been on combining targeted therapies with ICI for the purpose of manipulating the immune setpoint. The latter concept describes the equilibrium between factors that promote and those that suppress anti-cancer immunity. Besides tumor mutational load and other cancer cell-intrinsic determinants, the immune setpoint is also governed by the cells of the tumor microenvironment and how they are coerced by cancer cells to support the survival and growth of the tumor. These regulatory mechanisms provide therapeutic opportunities to intervene and reduce immune suppression via application of small molecule inhibitors and antibody-based therapies against (receptor) tyrosine kinases and thereby improve the response to ICIs. This article reviews how tyrosine kinase signaling in the tumor microenvironment can promote immune suppression and highlights how therapeutic strategies directed against specific tyrosine kinases can be used to lower the immune setpoint and elicit more effective anti-tumor immunity.

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Section: Immune Checkpoint Inhibitorsmentioning

confidence: 99%

Enhancing therapeutic anti-cancer responses by combining immune checkpoint and tyrosine kinase inhibition

et al. 2022

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“…Many trials have focused on antibodies blocking PD-1/PD-L1 and CTLA-4 as single agents or in combinations in B-NHL patients ( 134 ). Ipilimumab is an anti-CTLA-4 antibody that is approved to treat metastatic melanoma and several other tumor types ( 135 ). Studies in patients with solid tumors indicated that ipilimumab treatment depleted intratumoral Tregs possibly through antibody-dependent cell mediated cytotoxicity ( 136 ).…”

Section: Impact Of Targeted Therapiesmentioning

confidence: 99%

Regulatory T cells (Tregs) in lymphoid malignancies and the impact of novel therapies

et al. 2022

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Regulatory T cells (Tregs) are responsible for maintaining immune homeostasis by controlling immune responses. They can be characterized by concomitant expression of FoxP3, CD25 and inhibitory receptors such as PD-1 and CTLA-4. Tregs are key players in preventing autoimmunity and are dysregulated in cancer, where they facilitate tumor immune escape. B-cell lymphoid malignancies are a group of diseases with heterogenous molecular characteristics and clinical course. Treg levels are increased in patients with B-cell lymphoid malignancies and correlate with clinical outcomes. In this review, we discuss studies investigating Treg immunobiology in B-cell lymphoid malignancies, focusing on clinical correlations, mechanisms of accumulation, phenotype, and function. Overarching trends suggest that Tregs can be induced directly by tumor cells and recruited to the tumor microenvironment where they suppress antitumor immunity to facilitate disease progression. Further, we highlight studies showing that Tregs can be modulated by novel therapeutic agents such as immune checkpoint blockade and targeted therapies. Treg disruption by novel therapeutics may beneficially restore immune competence but has been associated with occurrence of adverse events. Strategies to achieve balance between these two outcomes will be paramount in the future to improve therapeutic efficacy and safety.

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“…In the analysis of immune checkpoint gene expression in the HRisk and LRisk groups, we found that PDL-1 was highly expressed in the HRisk group, and that highly expressed PDL-1 could inhibit the migration and proliferation of T cells by binding to PD-1 of T cells, thus inducing tumour tolerance and T-cell failure. Anti-PD-1 could significantly reverse this process to restore the anticancer function of T cells ( 42 ); therefore, the HRisk group was more sensitive to anti-PD-1 treatment. The above results suggest that treatment with paclitaxel combined with anti-PD-1 in the HRisk group may lead to better therapeutic outcomes.…”

Section: Discussionmentioning

confidence: 99%

Based on different immune responses under the glucose metabolizing type of papillary thyroid cancer and the response to anti-PD-1 therapy

Xie

Zeng

et al. 2022

Front. Immunol.

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Glucose metabolism-related genes play an important role in the development and immunotherapy of many tumours, but their role in thyroid cancer is ambiguous. To investigate the role of glucose metabolism-related genes in the development of papillary thyroid cancer (PTC) and their correlation with the clinical outcome of PTC, we collected transcriptomic data from 501 PTC patients in the Cancer Genome Atlas (TCGA). We performed nonnegative matrix decomposition clustering of 2752 glucose metabolism-related genes from transcriptome data and classified PTC patients into three subgroups (C1 for high activation of glucose metabolism, C2 for low activation of glucose metabolism and C3 for moderate activation of glucose metabolism) based on the activation of different glucose metabolism-related genes in 10 glucose metabolism-related pathways. We found a positive correlation between the activation level of glucose metabolism and the tumour mutation burden (TMB), neoantigen number, mRNA stemness index (mRNAsi), age, and tumour stage in PTC patients. Next, we constructed a prognostic prediction model for PTC using six glucose metabolism-related genes (PGBD5, TPO, IGFBPL1, TMEM171, SOD3, TDRD9) and constructed a nomogram based on the risk score and clinical parameters of PTC patients. Both the prognostic risk prediction model and nomogram had high stability and accuracy for predicting the progression-free interval (PFI) in PTC patients. Patients were then divided into high-risk and low-risk groups by risk score. The high-risk group was sensitive to paclitaxel and anti-PD-1 treatment, and the low-risk group was sensitive to sorafenib treatment. We found that the high-risk group was enriched in inflammatory response pathways and associated with high level of immune cell infiltration. To verify the accuracy of the prognostic prediction model, we knocked down PGBD5 in PTC cells and found that the proliferation ability of PTC cells was significantly reduced. This suggests that PGBD5 may be a relatively important oncogene in PTC. Our study constructed a prognostic prediction model and classification of PTC by glucose metabolism-related genes, which provides a new perspective on the role of glucose metabolism in the development and immune microenvironment of PTC and in guiding chemotherapy, targeted therapy and immune checkpoint blockade therapy of PTC.

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Immune Checkpoint Inhibitors in Cancer Therapy

Cited by 341 publications

References 147 publications

Enhancing therapeutic anti-cancer responses by combining immune checkpoint and tyrosine kinase inhibition

Enhancing therapeutic anti-cancer responses by combining immune checkpoint and tyrosine kinase inhibition

Regulatory T cells (Tregs) in lymphoid malignancies and the impact of novel therapies

Based on different immune responses under the glucose metabolizing type of papillary thyroid cancer and the response to anti-PD-1 therapy

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