Does CCL19 act as a double-edged sword in cancer development?

Abstract

Cancer is considered a life-threatening disease, and several factors are involved in its development. Chemokines are small proteins that physiologically exert pivotal roles in lymphoid and non-lymphoid tissues. The imbalance or dysregulation of chemokines has contributed to the development of several diseases, especially cancer. CCL19 is one of the homeostatic chemokines that is abundantly expressed in the thymus and lymph nodes. This chemokine, which primarily regulates immune cell trafficking, is involved in cancer development. Through the induction of anti-tumor immune responses and inhibition of angiogenesis, CCL19 exerts tumor-suppressive functions. In contrast, CCL19 also acts as a tumor-supportive factor by inducing inflammation, cell growth, and metastasis. Moreover, CCL19 dysregulation in several cancers, including colorectal, breast, pancreatic, and lung cancers, has been considered a tumor biomarker for diagnosis and prognosis. Using CCL19-based therapeutic approaches has also been proposed to overcome cancer development. This review will shed more light on the multifarious function of CCL19 in cancer and elucidate its application in diagnosis, prognosis, and even therapy. It is expected that the study of CCL19 in cancer might be promising to broaden our knowledge of cancer development and might introduce novel approaches in cancer management.

Keywords: CCL19; biomarker; cancer; chemokine; immunotherapy.

Graphical Abstract

Fig. 1

Schematic illustration of CCL19’s involvement in cancer development. The tumor-suppressive role of CCL19 (shown in the blue area) relies on the enhancement of anti-tumor responses and inhibition of angiogenesis. In contrast, the tumor-promoting role of CCL19 (shown in the red area) is attributed to the inhibition of cell apoptosis, promotion of metastasis and tumor heterogeneity, and inflammation.