Chronic inflammation, cancer development and immunotherapy

Abstract

Chronic inflammation plays a pivotal role in cancer development. Cancer cells interact with adjacent cellular components (pro-inflammatory cells, intrinsic immune cells, stromal cells, etc.) and non-cellular components to form the inflammatory tumor microenvironment (TME). Interleukin 6 (IL-6), macrophage migration inhibitory factor (MIF), immune checkpoint factors and other pro-inflammatory cytokines produced by intrinsic immune cells in TME are the main mediators of intercellular communication in TME, which link chronic inflammation to cancer by stimulating different oncogenic signaling pathways and improving immune escape to promote cancer development. In parallel, the ability of monocytes, T regulatory cells (Tregs) and B regulatory cells (Bregs) to perform homeostatic tolerogenic functions is hijacked by cancer cells, leading to local or systemic immunosuppression. Standard treatments for advanced malignancies such as chemotherapy and radiotherapy have improved in the last decades. However, clinical outcomes of certain malignant cancers are not satisfactory due to drug resistance and side effects. The clinical application of immune checkpoint therapy (ICT) has brought hope to cancer treatment, although therapeutic efficacy are still limited due to the immunosuppressive microenvironment. Emerging evidences reveal that ideal therapies including clearance of tumor cells, disruption of tumor-induced immunosuppression by targeting suppressive TME as well as reactivation of anti-tumor T cells by ICT. Here, we review the impacts of the major pro-inflammatory cells, mediators and their downstream signaling molecules in TME on cancer development. We also discuss the application of targeting important components in the TME in the clinical management of cancer.

Carcinogenic effect of human tumor-derived cell-free filtrates in nude mice

“…Melanoma-derived CFFs presented the highest concentrations of H 2 O 2 and IL-6, IL-1, TNFα, and Sirtuin 1. These are all well-renown tumor biomarkers with a definitive role in carcinogenesis promotion, malignant progression, cancer invasiveness, chemotherapy resistance, and metastasis, and, in general, correlate with a worse prognosis ( Berraondo et al, 2019 ; Costa-Machado and Fernandez-Marcos, 2019 ; Yang et al, 2020 ; Propper and Balkwill, 2022 ; Wen et al, 2022 ). Conversely, most of these biomarkers were not detected in control healthy skin-derived homogenates.…”

The role of tumor-associated macrophages in tumor immune evasion

“…Tregs and MDSCs are identified as significant components of the regulatory networks that facilitate tumor immune escape, significantly compromising the efficacy of current immunotherapies (Facciabene et al 2012 ; Lv et al 2022 ). Their presence and activity within the TME can hinder the ability of the immune system to effectively target and eliminate tumor cells, posing a significant challenge to the development and success of immunotherapeutic strategies (Hatziioannou et al 2017 ; Wen et al 2022 ).…”

Beyond Small Molecules: Antibodies and Peptides for Fibroblast Activation Protein Targeting Radiopharmaceuticals

“…This microenvironment encompasses not only cancerous cells but also vital constituents like the extracellular matrix [ 7 , 8 , 9 , 10 ], stromal cells [ 11 , 12 , 13 ], and immune cells [ 14 , 15 , 16 ], forming the tumor microenvironment (TME) [ 17 , 18 , 19 , 20 ]. The TME, an intricate milieu unique to tumors, exerts profound influences on tumor progression, immune evasion, metastasis, and therapeutic resistance [ 4 , 21 , 22 , 23 , 24 , 25 , 26 ].…”