AACR 2023: Respiratory Viral Infections and Proliferation of Breast Cancer

By: Amanda E. Ruffino, BA
Posted: Monday, May 8, 2023

The study of chronic inflammation in the setting of cancer is well established; however, the role of respiratory viral infections on tumorigenesis is poorly defined. Venkataswarup Tiriveedhi, PhD, and Umer Ali (a PhD student), both of Tennessee State University, Nashville investigated the impact of respiratory viral infections on breast cancer progression. They presented their findings at the American Association for Cancer Research (AACR) Annual Meeting 2023 (Abstract 341/21).

Murine respiratory epithelial cells were infected with murine Sendai virus and co-cultured with 4T1 murine breast cancer cells in both direct and trans-well formats. The results showed a 40% to 80% increase in breast cancer cell proliferation (P < .05). The supernatant collected from infected murine respiratory epithelial cells also induced a 2.3-fold increase in breast cancer cell proliferation. The cytokine analysis of the supernatant revealed a 17- to 23-fold increase in α/β-secretion.

Further experiments showed that α-defensin and β-defensin-3 enhanced the expression of chemokine metastatic receptor (CXCR4), angiogenic factor (VEGF), and cell division favoring factor (CDK2). The infected murine respiratory epithelial cells showed upregulation of Toll-like receptor 2 (TLR2) and NOD-like receptor protein 3 (NLRP3) expression, indicating a potential role for these receptors in respiratory viral infection–induced breast cancer progression. Co-culturing infected murine respiratory epithelial cells with murine CD4 T cells induced an exhaustion phenotype (PD-1–positive and CTLA-4–positive differentiation of CDR T cells), which inhibited antitumor adaptive immune responses.

The investigators have underscored the critical role of α/β-defensins and highlighted the mechanisms underlying the association in respiratory viral infection–induced breast cancer progression. These findings suggest that respiratory viral infections may promote breast cancer proliferation by inducing cancer cell proliferation and inhibiting antitumor adaptative immune responses. These findings also suggest that targeting defensins or their receptors may be a potential strategy for preventing respiratory viral infection–induced breast cancer progression. 

Disclosure: The study authors reported no conflicts of interest.

AACR Annual Meeting 2023

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