Imaging tumor-stroma interactions during chemotherapy reveals contributions of the microenvironment to resistance

Area of Science:

• Oncology
• Cancer Biology
• Tumor Microenvironment Research

Background:

• The tumor microenvironment's role in cancer therapy response remains poorly understood.
• Dynamics of cancer cell death and drug distribution in vivo are challenging to study.

Purpose of the Study:

• To investigate the impact of the tumor microenvironment on cancer cell death dynamics during chemotherapy.
• To explore the relationship between vascular permeability, immune cell infiltration, and therapeutic outcomes in mouse mammary carcinomas.

Main Methods:

• Intravital microscopy was employed to visualize drug distribution, cell death, and tumor-stroma interactions in chemotherapy-treated mouse mammary carcinomas.
• Genetic manipulation (matrix metalloproteinase-9 null and Ccr2 null mice) was used to assess the roles of vascular leakage and myeloid cell infiltration.

Main Results:

• Increased vascular leakage correlated with improved response to doxorubicin, particularly in matrix metalloproteinase-9 null mice.
• Chemokine (C-C motif) receptor 2 (CCR2)-dependent myeloid cell infiltration was observed post-treatment.
• Ccr2 null host mice exhibited enhanced responses to doxorubicin and cisplatin treatments.

Conclusions:

• The tumor microenvironment critically regulates drug response through vascular permeability and innate immune cell infiltration.
• Live imaging techniques offer valuable insights into drug responses within the tumor microenvironment in situ.
• Targeting vascular permeability and myeloid cell infiltration presents potential therapeutic strategies for improving cancer treatment efficacy.