The cytokines in tumor microenvironment: from cancer initiation-elongation-progression to metastatic outgrowth.

It is a well-known fact that cancer can be augmented by infections and inflammation. In fact, chronic inflammation establishes a tumor-supporting-microenvironment (TME), which contributes to neoplastic progression. Presently, extensive research is going on to establish the interrelationship between infection, inflammation, immune response, and cancer. Cytokines are the most essential components in this linkage, which are secreted by immune cells and stromal cells of TME. Cytokines have potential involvement in tumor initiation, elongation, progression, metastatic outgrowth, angiogenesis, and development of therapeutic resistance. They are also linked with increased cancer symptoms along with reduced quality of life in advanced cancer patients. The cancer patients experience multiple symptoms including pain, asthenia, fatigue, anorexia, cachexia, and neurodegenerative disorders etc. Anti-cancer therapeutics can be developed by targeting cytokines along with TME to reduce the immunocompromised state and also modulate the TME. This review article depicts the composition and function of different inflammatory cells within the TME, more precisely the role of cytokines in cancer initiation, elongation, and progression as well as the clinical effects in advanced cancer patients. It also provides an overview of different natural compounds, nanoparticles, and chemotherapeutic agents that can target cytokines along with TME, which finally pave the way for cytokines-targeted anti-cancer therapeutics.