Recent updates on cancer immunotherapy

Liu, Ming; Guo, Fukun

doi:10.1093/pcmedi/pby011

Cited by 105 publications

(83 citation statements)

References 88 publications

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“…ICIs have shown considerable objective response rates (ORR), durable toxicities and even prolong the OS in several cancers, including advanced EC. However, the effective rates of singleagent were 31% in melanoma and only 17% in lung cancer, respectively (13). And the response rate of ICI alone in EC patients varied from 9.9 to 33.3% in the reported studies (14).…”

Section: The Ongoing Clinical Trials In Ecmentioning

confidence: 99%

The Combination Options and Predictive Biomarkers of PD-1/PD-L1 Inhibitors in Esophageal Cancer

Yang

Wang

et al. 2020

Front. Oncol.

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Esophageal cancer (EC) is one of the most common cancers with poor survival in the world. Nowadays, a generous number of clinical trials are underway on the use of immunotherapy in EC patients, especially the programmed death-1/programmed death-ligand 1 (PD-1/PD-L1) inhibitors. However, only a few patients could benefit from single-agent therapy. Others need combination therapies to enhance the response rate and survival. In this review, we focus on PD-1/PD-L1 inhibitors and its combination options in EC patients. We also summarized the potential predictive biomarkers for PD-1/PD-L1 inhibitors treatment.

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Section: The Ongoing Clinical Trials In Ecmentioning

confidence: 99%

The Combination Options and Predictive Biomarkers of PD-1/PD-L1 Inhibitors in Esophageal Cancer

Yang

Wang

et al. 2020

Front. Oncol.

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“…Cancer immunotherapy based on blockade of the programmed cell death protein 1 (PD-1)/PD-1 ligand 1 (PD-L1) pathway with monoclonal antibodies is increasingly applied in clinical practice [1][2][3][4]. Initially, pembrolizumab and nivolumab were approved by the Food and Drug Administration (FDA) in 2014 for the treatment of patients with advanced melanomas [4].…”

Section: Introductionmentioning

confidence: 99%

Abrogation of IFN-γ Signaling May not Worsen Sensitivity to PD-1/PD-L1 Blockade

Vackova

Piatakova

Poláková

et al. 2020

IJMS

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Programmed cell death protein 1 (PD-1)/PD-1 ligand 1 (PD-L1) blockade is a promising therapy for various cancer types, but most patients are still resistant. Therefore, a larger number of predictive biomarkers is necessary. In this study, we assessed whether a loss-of-function mutation of the interferon (IFN)-γ receptor 1 (IFNGR1) in tumor cells can interfere with anti-PD-L1 therapy. For this purpose, we used the mouse oncogenic TC-1 cell line expressing PD-L1 and major histocompatibility complex class I (MHC-I) molecules and its TC-1/A9 clone with reversibly downregulated PD-L1 and MHC-I expression. Using the CRISPR/Cas9 system, we generated cells with deactivated IFNGR1 (TC-1/dIfngr1 and TC-1/A9/dIfngr1). In tumors, IFNGR1 deactivation did not lead to PD-L1 or MHC-I reduction on tumor cells. From potential inducers, mainly IFN-α and IFN-β enhanced PD-L1 and MHC-I expression on TC-1/dIfngr1 and TC-1/A9/dIfngr1 cells in vitro. Neutralization of the IFN-α/IFN-β receptor confirmed the effect of these cytokines in vivo. Combined immunotherapy with PD-L1 blockade and DNA vaccination showed that IFNGR1 deactivation did not reduce tumor sensitivity to anti-PD-L1. Thus, the impairment of IFN-γ signaling may not be sufficient for PD-L1 and MHC-I reduction on tumor cells and resistance to PD-L1 blockade, and thus should not be used as a single predictive marker for anti-PD-1/PD-L1 cancer therapy.

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“…In recent years, immunotherapy has revolutionized the way we treat cancer and been recognized as one of the four pillars of cancer treatment alongside surgery, chemotherapy and radiotherapy [132,133]. Current immunotherapy mainly relies on antibodies that block the ligation of inhibitory receptors Cells 2020, 9, 1181 9 of 18 such as PD-1, allowing tumor-infiltrating CD8 T cells to exhibit its cytotoxicity capacity against tumor cells.…”

Section: The Inhibitory Receptors On γδ T Cells and Cancer Immunotherapymentioning

confidence: 99%

The Aging of γδ T Cells

Lau

Fülöp

et al. 2020

Cells

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In the coming decades, many developed countries in the world are expecting the "greying" of their populations. This phenomenon poses unprecedented challenges to healthcare systems. Aging is one of the most important risk factors for infections and a myriad of diseases such as cancer, cardiovascular and neurodegenerative diseases. A common denominator that is implicated in these diseases is the immune system. The immune system consists of the innate and adaptive arms that complement each other to provide the host with a holistic defense system. While the diverse interactions between multiple arms of the immune system are necessary for its function, this complexity is amplified in the aging immune system as each immune cell type is affected differently-resulting in a conundrum that is especially difficult to target. Furthermore, certain cell types, such as γδ T cells, do not fit categorically into the arms of innate or adaptive immunity. In this review, we will first introduce the human γδ T cell family and its ligands before discussing parallels in mice. By covering the ontogeny and homeostasis of γδ T cells during their lifespan, we will better capture their evolution and responses to age-related stressors. Finally, we will identify knowledge gaps within these topics that can advance our understanding of the relationship between γδ T cells and aging, as well as age-related diseases such as cancer.Their well-characterized roles further imply the physiological importance of age-associated T-cell adaptations, which garners the widespread scientific interest that has contributed to the current depth of T-cell-related investigations [14,15].T cells can essentially be classified into the adaptive arm, although minority subsets exhibit an innate phenotype. Adaptive T cells include those expressing an αβ T cell receptor (TCR) at their surface and "innate-like" T cells are comprised of T cells expressing a γδ TCR, mucosal associated invariant T (MAIT), invariant natural killer T (iNKT) and germline-encoded mycolyl lipid-reactive (GEMT) [16]. This classification is based on their response speed when encountering new antigens and the ability to form memory cells that persist in long-term immunosurveillance. In this review, we will focus on γδ T cells and their contextual importance in cancer immunosurveillance, and on the reactivation of latent infections such as tuberculosis and virus-infected cells, as these topics require consolidation in the literature but are often neglected in the aging context.First, we will describe γδ T cells and their respective ligands in both mice and human. Next, we will analyze γδ T cells from cradle to grave (i.e., development to old age) to understand their aging trajectory during lifespan. Finally, we will suggest future developments that are necessary for our comprehension of how γδ T cells subsets are affected during the aging process. A better understanding of γδ T cell biology should enable scientists to tailor optimized immunotherapy that targets age-associated immune impairments in th...

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Recent updates on cancer immunotherapy

Cited by 105 publications

References 88 publications

The Combination Options and Predictive Biomarkers of PD-1/PD-L1 Inhibitors in Esophageal Cancer

The Combination Options and Predictive Biomarkers of PD-1/PD-L1 Inhibitors in Esophageal Cancer

Abrogation of IFN-γ Signaling May not Worsen Sensitivity to PD-1/PD-L1 Blockade

The Aging of γδ T Cells

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