Simultaneous blockade of the CD73/EGFR axis inhibits tumor growth

Abstract

Targeting the influencing factors in tumor growth and expansion in the tumor microenvironment is one of the key approaches to cancer immunotherapy. Various factors in the tumor microenvironment can in cooperation stimulate tumor growth, suppress anti-tumor immune responses, promote drug resistance, and ultimately enhance tumor recurrence. Therefore, due to the dependence and close cooperation of these axes, their combined targeting can have a greater effect compared to their individual targeting. Among the important factors affecting tumor growth in the tumor region, CD73 and EGFR play an important role in tumor growth by stimulating each other's expression and function. Therefore, we intended to use the nanocarriers that we had previously produced and characterized to deliver anti-CD73 and EGFR siRNAs to murine breast cancer 4T1 cells. Silencing CD73 and EGFR could significantly induce cell death in cancer cells. Downregulation of the CD73/EGFR axis also suppressed the migratory and proliferative potential of cancer cells. This therapeutic strategy also inhibited tumor growth in in ovo model. These findings imply that simultaneous targeting of CD73 and EGFR in breast cancer can be considered a novel immunotherapeutic approach that needs further investigation in future studies.