Immunotherapy in Advanced Gastric Cancer: An Overview of the Emerging Strategies

Magalhães, Helena; Fontes‐Sousa, Mário; Machado, Manuela

doi:10.1155/2018/2732408

Cited by 17 publications

(23 citation statements)

References 33 publications

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“…Gastric cancer (GC) is the fifth and third most common cancer and cause of cancer deaths worldwide, respectively (1). Although incidence and death rates are declining (131), advancements in prevention and treatment remain a priority.…”

Section: Gastric Cancermentioning

confidence: 99%

“…Gastrointestinal (GI) cancers are some of the most common cancers worldwide and a major cause of cancer-related deaths (1)(2)(3)(4)(5). Immune checkpoint inhibitors (ICIs), including pembrolizumab (Keytruda) and nivolumab (Opdivo), antibodies against programmed death-1 (PD-1), recently gained Food and Drug Administration (FDA) approval for use in GI cancers (Table 1) (6)(7)(8)(9)(10)(11).…”

Section: Introductionmentioning

confidence: 99%

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CD73's Potential as an Immunotherapy Target in Gastrointestinal Cancers

et al. 2020

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CD73, a cell surface 5 ′ nucleotidase that generates adenosine, has emerged as an attractive therapeutic target for reprogramming cancer cells and the tumor microenvironment to dampen antitumor immune cell evasion. Decades of studies have paved the way for these findings, starting with the discovery of adenosine signaling, particularly adenosine A2A receptor (A2AR) signaling, as a potent suppressor of tissue-devastating immune cell responses, and evolving with studies focusing on CD73 in breast cancer, melanoma, and non-small cell lung cancer. Gastrointestinal (GI) cancers are a major cause of cancer-related deaths. Evidence is mounting that shows promise for improving patient outcomes through incorporation of immunomodulatory strategies as single agents or in combination with current treatment options. Recently, several immune checkpoint inhibitors received FDA approval for use in GI cancers; however, clinical benefit is limited. Investigating molecular mechanisms promoting immunosuppression, such as CD73, in GI cancers can aid in current efforts to extend the efficacy of immunotherapy to more patients. In this review, we discuss current clinical and basic research studies on CD73 in GI cancers, including gastric, liver, pancreatic, and colorectal cancer, with special focus on the potential of CD73 as an immunotherapy target in these cancers. We also present a summary of current clinical studies targeting CD73 and/or A2AR and combination of these therapies with immune checkpoint inhibitors.

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Section: Gastric Cancermentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

CD73's Potential as an Immunotherapy Target in Gastrointestinal Cancers

et al. 2020

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“…For GC treatment, besides surgical treatment, radiotherapy and chemotherapy are still frequently used adjuvant treatment methods ( 4 ). Immunotherapy has received great interest in recent years; however, it has not become a major treatment option for GC ( 5 ). Tumor immunotherapy is gaining significant popularity in the field of cancer treatment, benefiting from the in-depth study of cancer immunosuppression in recent years ( 5 ).…”

Section: Introductionmentioning

confidence: 99%

Interaction between regulatory T cells and mast cells via IL‑9 and TGF‑β production

et al. 2020

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Research on the immunosuppression of cancer cells has attracted much attention in recent years. The present study sought to provide a new strategy for tumor immunotherapy targeting mast cells by studying the mechanisms underlying mast cell function in cancer immunosuppression. Between January 2015 and December 2017, the tumor tissues of 40 patients with gastric cancer (GC) were collected and grouped in Lihuili Hospital of Ningbo City, China. Pathological sections were prepared and an immunofluorescence assay was performed to analyze the expression of forkhead Box Protein P3 (FOXP3), tryptase, TGFβ1, TGF-βR, IL-9, IL-9R and Oxford 40 ligand (OX40L). Then, the correlations between FOXP3 and tryptase, TGFβ1 and tryptase expression, and the expression of OX40L in patients with GC with different stages were analyzed. The results revealed that high levels of mast cells were present in patients GC, and tryptase and FOXP3 expressions were positively correlated. Mast cells regulate T regulatory (reg) cells in the gastric tumor microenvironment by secreting TGFβ1. Tregs, in turn, promote the survival of mast cells in the tumor microenvironment by producing IL-9. Furthermore, OX40L expression in mast cells was significantly associated with Tumor-Node-Metastasis staging of GC. Overall, the present study reported a positive feedback system that functions through TGFβ1 and IL-9 to allow cross-talk between Tregs and mast cells. Moreover, OX40L may be a potential target for the diagnosis and treatment of GC. These results may provide a new strategy for tumor immunotherapy targeting mast cells.

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“…Их эффективность была оценена во второй фазе клинических испытаний при РЖ/КЭР. За исключением единичных случаев, ни один из препаратов не продемонстрировал значимого эффекта [47].…”

Section: иммунотерапия рака желудкаunclassified

Promising Targeted Therapies Genes and Prognostic Biomarkers of Gastric Cancer

et al. 2018

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Understanding the molecular genetic features of gastric cancer (GC) and principally the functioning of signaling cascades involved in its occurrence and development is determining for identifying the most promising genes for targeted therapy. On this basis, development and consequent implementation of effective drugs and treatment regimens is conducted. The inductors of signaling paths, the main one of which is the mTOR pathway, and the functioning of the pathway are considered in details. mTOR inductors (angiogenesis factors, epidermal growth factor and their receptors) are most actively studied as therapeutic targets. Particular attention is paid to the consideration of stimulation and development of lymphangiogenesis where not all genes are discovered and examined yet. The possibility of achieving a significant therapeutic effect with simultaneous inhibition of the action of genes of angio- and lymphangiogenesis is considered. The review covers the administered target drugs and pharmaceuticals under investigation for GC therapy, including immunotherapy. The review provides details on the simultaneous activation of several genes ― potential targets of therapy and possible interactions in the development of the tumor process. As a result the combined effect of the simultaneous action of two or more factors can be detected. The possibility of maintaining the activated signaling cascade when one of the activated receptors is blocked in consequence of the action of another expressed receptor is also considered. The article presents information on development of drugs affecting several targets and on effectiveness of combined therapy with different targeted drugs. Essential effectiveness of GC therapy can be achieved by personified treatment including application of molecular classification. The review discusses the prognostic value of target and other genes expression, as well as GC subtypes according molecular classification.

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Immunotherapy in Advanced Gastric Cancer: An Overview of the Emerging Strategies

Cited by 17 publications

References 33 publications

CD73's Potential as an Immunotherapy Target in Gastrointestinal Cancers

CD73's Potential as an Immunotherapy Target in Gastrointestinal Cancers

Interaction between regulatory T cells and mast cells via IL‑9 and TGF‑β production

Promising Targeted Therapies Genes and Prognostic Biomarkers of Gastric Cancer

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Immunotherapy in Advanced Gastric Cancer: An Overview of the Emerging Strategies

Cited by 17 publications

References 33 publications

CD73's Potential as an Immunotherapy Target in Gastrointestinal Cancers

CD73's Potential as an Immunotherapy Target in Gastrointestinal Cancers

Interaction between regulatory T cells and mast cells via IL‑9 and TGF‑&beta; production

Promising Targeted Therapies Genes and Prognostic Biomarkers of Gastric Cancer

Contact Info

Product

Resources

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Interaction between regulatory T cells and mast cells via IL‑9 and TGF‑β production