Checkpoints and beyond – Immunotherapy in colorectal cancer

Gutting, Tobias; Burgermeister, Elke; Härtel, Nicolai; Ebert, Matthias

doi:10.1016/j.semcancer.2018.04.003

Cited by 33 publications

(25 citation statements)

References 157 publications

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“…Treatment for CRC is based largely on the cancer stage (extent) and the implementation of novel treatment modalities have significantly improved the management of CRC, with surgery remaining as the main pillar. Radiation and chemotherapies may also be used before or after surgery (Banerjee et al, 2017; Ratnapradipa et al, 2017; São Julião et al, 2017), while immunotherapy arises as a novel promising therapeutic approach for this pathology (Gutting et al, 2018). The role of histamine and histamine receptors in this cancer subtype has been more extensively investigated than in gastric, esophageal or liver cancer (reviewed in Medina and Rivera, 2010; Massari et al, 2019).…”

Section: Clinicopathological Characteristics Of H4r In Gastrointestinmentioning

confidence: 99%

Pathophysiological Role of Histamine H4 Receptor in Cancer: Therapeutic Implications

2019

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Cancer is a leading cause of death in both developed and developing countries. Although advances in cancer research lead to improved anti-neoplastic therapies, they continue to have unfavorable outcomes, including poor response and severe toxicity. Thus, the challenge for the new therapeutic approaches is to increase anti-tumor efficacy by targeting different molecules encompassed in the tumor and its microenvironment, as well as their specific interactions. The histamine H4 receptor (H4R) is the last discovered histamine receptor subtype and it modulates important immune functions in innate and in adaptive immune responses. Several ligands have been developed and some of them are being used in clinical trials for immune disorders with promising results. When searched in The Cancer Genome Atlas (TCGA) database, human H4R gene was found to be expressed in bladder cancer, kidney cancer, breast cancer, gastrointestinal cancers, lung cancer, endometrial cancer, and skin cancer. In the present work, we aimed to briefly summarize current knowledge in H4R’s pharmacology and in the clinical use of H4R ligands before focusing on recent data reporting the expression of H4R and its pathophysiological role in cancer, representing a potential molecular target for cancer therapeutics. H4R gene and protein expression in different types of cancers compared with normal tissue as well as its relationship with patient prognosis in terms of survival will be described.

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Section: Clinicopathological Characteristics Of H4r In Gastrointestinmentioning

confidence: 99%

Pathophysiological Role of Histamine H4 Receptor in Cancer: Therapeutic Implications

2019

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“…Surgery and chemotherapy are the major treatment approaches for CRC; however, their effect is unsatisfactory in patients with distant metastases. This poor effect can be attributed to a suppressed immune system that lacks an effective anti-tumor activity [3,4]. The human immune system is composed of many immune cells.…”

Section: Introductionmentioning

confidence: 99%

Prognostic value of peripheral blood natural killer cells in colorectal cancer

Tang

Xie

et al. 2020

BMC Gastroenterol

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Background: The association between natural killer (NK) cells and survival in colorectal cancer (CRC) patients remains controversial. This study aimed to clarify the prognostic value of peripheral blood NK cells in CRC patients.Methods: A total of 447 CRC patients who underwent radical surgery and chemotherapy were retrospectively analyzed. Cox regression analyses were used to identify independent prognostic indicators. Correlation between NK cell percentage and other clinicopathological features (gender, age, histological grade, tumor stage, immune cells, and inflammatory indicators) was analyzed. The prognostic values of the combinations of NK cell percentage and other clinicopathological features were also determined. Results: Multivariate Cox regression analysis revealed that NK cell percentage in the peripheral blood was an independent prognostic indicator in CRC patients. A higher percentage of NK cells indicated a longer survival time than a lower percentage. NK cell percentage was positively correlated to the T and B lymphocyte counts and negatively correlated to the patients' age and albumin levels. With an area of 0.741 under a receiver operating characteristic curve, NK cells have a moderate predictive value for 3rd-year survival in CRC. This area increased to 0.851 by combining NK cell percentage with the B lymphocyte count. Elderly patients and those at an advanced clinical stage presented a lower percentage of NK cells than younger patients and those at an early clinical stage.Conclusions: This study demonstrated that NK cells in the blood were an independent predictor of survival in CRC patients, and the combined count of NK cells and B lymphocytes could increase the prognostic value.

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“…Surgery remains the mainstay of treatment for colon cancer, but the use of laparoscopic approaches varies widely despite the demonstration of its short‐ and long‐term benefits (Ratnapradipa et al ., 2017). Immunotherapy is a novel promising approach for CRC (Gutting et al ., 2018).…”

Section: Introductionmentioning

confidence: 99%

Histamine receptors and cancer pharmacology: an update

Massari

Nicoud

Medina

2018

British J Pharmacology

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In the present review, we will discuss the recent advances in the understanding of the role of histamine and histamine receptors in cancer biology. The controversial role of the histaminergic system in different neoplasias including gastric, colorectal, oesophageal, oral, pancreatic, liver, lung, skin, blood and breast cancers will be reviewed. The expression of histamine receptor subtypes, with special emphasis on the histamine H4 receptor, in different cell lines and human tumours, the signal transduction pathways and the associated biological responses as well as the in vivo treatment of experimental tumours with pharmacological ligands will be described. The presented evidence demonstrates that histamine regulates cancer‐associated biological processes during cancer development in multiple cell types, including neoplastic cells and cells in the tumour micro‐environment. The outcome will depend on tumour cell type, the level of expression of histamine receptors, signal transduction associated with these receptors, tumour micro‐environment and histamine metabolism, reinforcing the complexity of cancer disease. Findings show the pivotal role of H4 receptors in the development and progression of many types of cancers, and considering its immunomodulatory properties, the H4 receptor appears to be the most promising molecular therapeutic target for cancer treatment within the histamine receptor family. Furthermore, the H4 receptor is differentially expressed in tumours compared with normal tissues, and in most cancer types in which data are available, H4 receptor expression is associated with clinicopathological characteristics, suggesting that H4 receptors might represent a novel cancer biomarker. Linked Articles This article is part of a themed section on New Uses for 21st Century. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v177.3/issuetoc

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Checkpoints and beyond – Immunotherapy in colorectal cancer

Cited by 33 publications

References 157 publications

Pathophysiological Role of Histamine H4 Receptor in Cancer: Therapeutic Implications

Pathophysiological Role of Histamine H4 Receptor in Cancer: Therapeutic Implications

Prognostic value of peripheral blood natural killer cells in colorectal cancer

Histamine receptors and cancer pharmacology: an update

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