The New Era of Immunotherapy in Gastric Cancer

Takei, Shogo; Kawazoe, Akihito; Shitara, Kohei

doi:10.3390/cancers14041054

Cited by 100 publications

(85 citation statements)

References 90 publications

(114 reference statements)

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“…Different ICI have been developed and approved to block PD-1/PD-L1 interaction and multiple clinical trials are still ongoing [139]. All the approved anti-PD-1 ICIs (pembrolizumab, nivolumab, cemiplimab and dostarlimab) are full-length antibodies and the developed radiopharmaceuticals are derived thereof [140,141].…”

Section: Pd-1mentioning

confidence: 99%

Radionuclide Imaging of Cytotoxic Immune Cell Responses to Anti-Cancer Immunotherapy

et al. 2022

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Cancer immunotherapy is an evolving and promising cancer treatment that takes advantage of the body’s immune system to yield effective tumor elimination. Importantly, immunotherapy has changed the treatment landscape for many cancers, resulting in remarkable tumor responses and improvements in patient survival. However, despite impressive tumor effects and extended patient survival, only a small proportion of patients respond, and others can develop immune-related adverse events associated with these therapies, which are associated with considerable costs. Therefore, strategies to increase the proportion of patients gaining a benefit from these treatments and/or increasing the durability of immune-mediated tumor response are still urgently needed. Currently, measurement of blood or tissue biomarkers has demonstrated sampling limitations, due to intrinsic tumor heterogeneity and the latter being invasive. In addition, the unique response patterns of these therapies are not adequately captured by conventional imaging modalities. Consequently, non-invasive, sensitive, and quantitative molecular imaging techniques, such as positron emission tomography (PET) and single-photon emission computed tomography (SPECT) using specific radiotracers, have been increasingly used for longitudinal whole-body monitoring of immune responses. Immunotherapies rely on the effector function of CD8+ T cells and natural killer cells (NK) at tumor lesions; therefore, the monitoring of these cytotoxic immune cells is of value for therapy response assessment. Different immune cell targets have been investigated as surrogate markers of response to immunotherapy, which motivated the development of multiple imaging agents. In this review, the targets and radiotracers being investigated for monitoring the functional status of immune effector cells are summarized, and their use for imaging of immune-related responses are reviewed along their limitations and pitfalls, of which multiple have already been translated to the clinic. Finally, emerging effector immune cell imaging strategies and future directions are provided.

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Section: Pd-1mentioning

confidence: 99%

Radionuclide Imaging of Cytotoxic Immune Cell Responses to Anti-Cancer Immunotherapy

et al. 2022

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“…Clinical trials of ICIs have displayed efficacy and safety for cancer patients (12,13). Notably, several ICIs such as pembrolizumab, avelumab, sintilimab, tislelizumab and ipilimumab have been approved for clinical application in combination with targeted therapy for treatment of advanced gastric tumour (14,15).…”

Section: Introductionmentioning

confidence: 99%

Recent Progress and Future Perspectives of Immunotherapy in Advanced Gastric Cancer

et al. 2022

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As one of the most common forms of solid tumours, gastric carcinoma has been revealed as the third leading cause of death worldwide. The symptom of gastric cancer is usually not obvious and thus difficult to detect at earlier stages. Therefore, gastric cancer is already in the advanced stage once detected in patients, which has a poor prognosis due to ineffective therapies and multiple resistance. Recent advance in understanding the microenvironment of cancer has significantly promoted the development of immunotherapy for advanced gastric cancer. Immunotherapy can induce immune responses in gastric cancer patients thus leads to the destruction of cancer cells. In comparison of traditional therapy, immunotherapy has demonstrated robust efficacy and tolerable toxicity. Therefore, this novel strategy for treatment of advanced gastric cancer has gain increasingly popularity. In this review, we summarize recent progress of immunotherapy in advanced gastric cancer, such as immune check point inhibitors, adoptive cell therapy, VEGF inhibitors, cancer vaccines and CAR-T cell therapy. We highlight immunotherapies involved in clinical applications and discuss the existing challenges of current immunotherapies and promising strategies to overcome these limitations.

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“…It achieves a therapeutic effect by inducing, enhancing or regulating immune response. Immunotherapy for gastric cancer currently consists primarily of immune checkpoint inhibitor therapy ( 7 , 8 ).…”

Section: Introductionmentioning

confidence: 99%

Expression profiles of m6A RNA methylation regulators, PD-L1 and immune infiltrates in gastric cancer

Chen¹,

Shu²,

Zhang

et al. 2022

Front. Oncol.

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Gastric cancer is the fourth most frequent cancer and has a high death rate. Immunotherapy represented by PD-1 has brought hope for the treatment of advanced gastric cancer. Methylation of the m6A genes is linked to the onset and progression of numerous cancers, but there are few studies on gastric cancer. The main purpose of this study aims to analyze the relationship between m6A RNA methylation regulators, PD-L1, prognosis and tumor immune microenvironment (TIME) in gastric cancer. The Cancer Genome Atlas (TCGA) and Genotype Tissue Expression (GTEx) databases were used to acquire transcriptomic data and clinical information from gastric cancer patients. The changes in m6A regulator expression levels in gastric cancer tissues and normal tissues were studied. Consensus clustering analysis was used to separate gastric cancer samples into two categories. We employed Least Absolute Shrinkage, Selection Operator (LASSO) Cox regression analysis, Gene Set Enrichment Analysis (GSEA), and cBioPortal to analyze the m6A regulators, PD-L1 and TIME in gastric cancer. In gastric cancer tissues, the majority of m6A regulatory factors are considerably overexpressed. Two gastric cancer subgroups (Cluster1/2) based on consensus clustering of 21 m6A regulators. PD-L1 and PD-1 expression levels were significantly higher in gastric cancer tissues, and they were significantly linked with METTL3, WTAP, HNRNPD, ZC3H7B, METTL14, FTO, PCIF1, HNRNPC, YTHDF1 and YTDHF2. Cluster1 showed a large increase in resting memory CD4+ T cells, regulatory T cells, naïve B cells, active NK cells, and resting Mast cells. Cluster1 and Cluster2 were shown to be involved in numerous critical signaling pathways, including base excision repair, cell cycle, nucleotide excision repair, RNA degradation, and spliceosome pathways. Gastric cancer RiskScores based on prognostic factors have been found as independent prognostic indicators. The amount of tumor-infiltrating immune cells is dynamically affected by changes in the copy number of m6A methylation regulators associated with TIME.

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The New Era of Immunotherapy in Gastric Cancer

Cited by 100 publications

References 90 publications

Radionuclide Imaging of Cytotoxic Immune Cell Responses to Anti-Cancer Immunotherapy

Radionuclide Imaging of Cytotoxic Immune Cell Responses to Anti-Cancer Immunotherapy

Recent Progress and Future Perspectives of Immunotherapy in Advanced Gastric Cancer

Expression profiles of m6A RNA methylation regulators, PD-L1 and immune infiltrates in gastric cancer

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