Chemokine clouding and liver cancer heterogeneity: Does it impact clinical outcomes?

Tumor heterogeneity is a predominant feature of hepatocellular carcinoma (HCC) that plays a crucial role in chemoresistance and limits the efficacy of available chemo/immunotherapy regimens. Thus, a better understanding regarding the molecular determinants of tumor heterogeneity will help in developing newer strategies for effective HCC management. Chemokines, a sub-family of cytokines are one of the key molecular determinants of tumor heterogeneity in HCC and are involved in cell survival, growth, migration, and angiogenesis. Herein, we provide a panoramic insight into the role of chemokines in HCC heterogeneity at genetic, epigenetic, metabolic, immune cell composition, and tumor microenvironment levels and its impact on clinical outcomes. Interestingly, our in-silico analysis data showed that expression of chemokine receptors impacts infiltration of various immune cell populations into the liver tumor and leads to heterogeneity. Thus, it is evident that aberrant chemokines clouding impacts HCC tumor heterogeneity and understanding this phenomenon in depth could be harnessed for the development of personalized medicine strategies in future.

Automated summary

Tumor heterogeneity is a crucial factor in the resistance to chemotherapy and limited efficacy in hepatocellular carcinoma (HCC). Chemokines, a sub-family of cytokines, play a key role in HCC heterogeneity by affecting cell survival, growth, migration, and angiogenesis. Understanding the impact of chemokines on genetic, epigenetic, metabolic, immune cell composition, and tumor microenvironment levels can contribute to the development of personalized medicine strategies for HCC.