Lung cancer development and progression are induced by genetic mutations and various factors, such as infections, environment, and lifestyle. Chemokines and their receptors play an important role in the growth and survival of tumor cells, and in cancer development and metastasis. In particular, CXCL13 (Chemokine ligand 13) and its related receptor, CXCR5 (Chemokine receptor 5), are reported to promote metastasis of lung cancer cells through signal transduction pathways, eventually leading to the development and progression of lung cancer. However, the molecular and cellular mechanisms of how CXCR5–CXCL13 functionally regulates lung cancer progression is insufficient.

Using data sets of NSCLC patients, we examined whether the expression of CXCR5 is associated with NSCLC progression. In addition, through molecular and cellular mechanism studies, we provided the functional evidence of CXCR5 in NSCLC progression via the CXCR5–CXCL13-TLR4 (Toll-like receptor 4) signaling axis for the activation of NF-κB (Figure 1). Since bacterial or viral infections play a pivotal role for the development and progression of NSCLC, our results strongly demonstrate that the CXCR5–CXCL13-TLR4 signaling axis might be a potential therapeutic target for the intervention of NSCLC patients with up-regulated CXCR5 and TLR4 in precision cancer medicine.

Jihye Shin (Sungkyunkwan University College of Medicine, combined master's and doctoral program), Dr. Mijeong Kim (BK21 FOUR young researcher, Sungkyunkwan University College of Medicine), and Jiyoung Kim (combined master's and doctoral program, Sungkyunkwan University College of Medicine) contributed to this study as the first authors.

Article: Shin JH, Kim MJ, Kim JY, Kang Y, Kim DH, Jeong SK, Chun E, Lee KY. CXCR5 and TLR4 signals synergistically enhance non-small cell lung cancer progression. Clin Transl Med (IF:10.6). 2024 Jan;14(1):e1547. doi: 10.1002/ctm2.1547. PMID: 38239075.

FIGURE 1. CXCR5 and TLR4 signals synergistically enhance lung cancer progression