The Role of Inflammation in Cancer: Mechanisms of Tumor Initiation, Progression, and Metastasis Original paper

What was studied?

This review investigates the role of inflammation in cancer biology, particularly its dual role in tumor initiation, progression, and metastasis. Inflammation is recognized as a critical factor in every stage of tumor development, from the initial genetic mutations to later phases like invasion and metastasis. The article examines how tumors create an inflammatory microenvironment that fosters angiogenesis, immune suppression, and malignant growth. It further explores how chronic inflammation, often triggered by infections, obesity, and environmental factors, accelerates tumorigenesis and metastasis. The review emphasizes the complexity of inflammation’s role, noting that while it can support tumor progression, it can also activate immune responses that are harnessed in cancer immunotherapy.

Who was studied?

The review synthesizes findings from clinical and preclinical studies on various cancer types, including colorectal, liver, breast, and esophageal cancers. It highlights how chronic inflammation, often induced by infections or autoimmune diseases, increases the risk of cancer. Studies included in the review examine how inflammatory mediators, such as cytokines (TNF-α, IL-6), oxidative stress, and reactive nitrogen species, contribute to genetic instability and tumor promotion. The role of specific immune cells, like tumor-associated macrophages (TAMs), regulatory T cells (Tregs), and myeloid-derived suppressor cells (MDSCs), in the tumor microenvironment (TME) is also explored, focusing on their contribution to immune suppression and tumor metastasis.

Most important findings

The review identifies inflammation as both a tumor promoter and a potential therapeutic target. It finds that chronic inflammation leads to DNA damage, epigenetic modifications, and genomic instability, all of which are key drivers of tumor initiation. Cytokines like TNF-α and IL-6 play a central role in promoting tumor survival and proliferation. These inflammatory signals activate transcription factors such as NF-κB and STAT3, which regulate genes involved in immune evasion, cell survival, and angiogenesis. Additionally, the review discusses how inflammatory cells within the TME interact with cancer cells, supporting tumor growth, metastasis, and therapy resistance. Notably, inflammation-driven angiogenesis and immune suppression foster a pro-tumor microenvironment that promotes metastasis and limits the effectiveness of conventional therapies.

Key implications

The findings of this review have significant implications for cancer therapy, especially in targeting the inflammatory pathways that drive tumor progression. Targeting specific inflammatory cytokines, such as TNF-α, IL-6, and IL-23, or their receptors could help mitigate tumor growth and metastasis. Moreover, strategies aimed at enhancing immune responses, such as through immune checkpoint inhibitors, could be used alongside anti-inflammatory therapies to improve cancer treatment outcomes. The review also suggests that managing inflammation could improve responses to chemotherapy and radiotherapy, as chronic inflammation often contributes to therapeutic resistance. These insights call for the development of therapeutic strategies that can selectively target the inflammatory pathways within the tumor microenvironment without compromising overall immune function.