Cytokines and Tumour Microenvironment
Tumour microenvironment (TME) refers to the non-cancerous cells and proteins present in the tumour that support the growth of cancerous cells. It is a key factor which contributes to the development of both primary and secondary tumours. Understanding how TME interacts with tumour and identifying changes in the TME during early stages of cancer can provide new important information for diagnosis, treatment, and preventing metastasis. In addition, modulating TME in favour of host resistance can maximize the efficacy of existing anti-cancer immunotherapies.
Interleukins and associated cytokines play a critical role in cancer development, growth, progression, spread, and control. As of November 2020, 88 antibody therapeutics are in the late-stage research, half of which are directed at combating cancer. During the past decades, numerous tumour researches have focused on:
• Interleukins in carcinogenesis
• Interleukins in the formation of tumour microenvironment
• Interleukin-based cancer control
These researches have demonstrated complex interactions among immune system, interleukins, and tumour cells and show the potential to exploit interleukins to develop and improve new cancer treatments.
We have selected some of the most exciting research papers recently published in these research directions.
Interleukins in cancer: from biology to therapy
This article reviewed more than 200 papers on the biological role of Interleukins in cancer development, progression and control, and the value of cytokines as cancer therapeutic targets. The authors also discussed how interleukins work in the tumour microenvironment. Furthermore, they highlighted a number of undergoing clinical trials that tested Interleukins in cancer therapy.
Research Target: Interleukins and associated cytokines
Read the full article in Nature Reviews Cancer, June 2021.
TGF-β signaling in Th17 cells promotes IL-22 production and colitis-associated colon cancer
As uncontrolled IL-22 has a protumorigenic effect, tight regulation of IL-22 is essential. The authors studied the effect of TGF-β signaling on the IL-22-producing T cells in colorectal cancer mouse samples. They found that TGF-β signaling CD4+ T cells (specifically Th17 cells) promote IL-22 production in Th17 cells.
Read the full article in Nature Communications, May 2020.
Elevated serum interleukin-8 is associated with enhanced intratumor neutrophils and reduced clinical benefit of immune-checkpoint inhibitors
This study used a large-scale retrospective analysis to elevate the association between the serum IL-8 levels and worse prognosis in patients with advanced cancers, who were treated with immune-checkpoint inhibitors. The authors found that IL-8 induced resistance to several immune checkpoint inhibitors and suggested serum IL-8 levels as an independent biomarker to identify unfavourable tumour immunobiology.
Research Target: IL-8
Read the full article inNature Mediicine, May 2020.
Tumor-initiating cells establish an IL-33-TGF- β niche signaling loop to promote cancer progression
In this study, the authors identified an IL-33-TGF- β niche signaling loop initiated by certain tumour cells within a specialized tumour microenvironment that become more invasive on exposure to transforming TGF-β. They also showed that the tumour cells release the cytokine IL-33, which can create a self-amplifying tumorigenic niche that promoting tumour cells’ malignant progression.
Research Target: TGF-β, IL-33
Read the full article inScience, July 2020.
Inhibition of IL-1β by canakinumab may be effective against diverse molecular subtypes of lung cancer: an exploratory analysis of the CANTOS trial
This article is an exploratory analysis of the CANTOS trial, targeting the patients, who had been diagnosed with lung cancer during the study. The authors segment these targeted patients by molecular characteristics and found that a substantial number of these patients already had circulating tumour DNA at the time of enrollment of the trial. These finding further reflected the importance of IL-1β-mediated protumour inflammation in diverse molecular subtypes of lung cancer.
Research Target: IL-1β
Read the full article in Cancer Research, December 2020.
The role of interleukin-17 in tumor development and progression
This article reviewed the role of IL-17 in cancer’s development, progression, and resistance to therapies, especially the IL-17 mediated inflammatory response and cancer promotion. The authors also discussed IL-17 in anticancer therapies and suggested further research on neutralizing IL-17 sensitizes resistant tumours to cancer immunotherapy.
Research Target: IL-17
Read the full article in Journal Experimental Medicine, November 2020.
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