Shaping of the Immune Landscape by Chemokine Receptors that Impacts the Clinical Outcome in Triple-Negative Breast Cancer

Chronic inflammation triggers a cytokine or chemokine storm in the tissue microenvironment. The unresolved, persistent inflammatory microenvironment has a tendency to initiate tumors or likely to favor the colonization of disseminated tumor cells (DTCs) into the inflamed tissue. Chemokines and their receptors present in the tumor cells and its microenvironment can orchestrate the progression of primary breast cancer and seed circulating tumor cells in distant organs such as the lungs. Chemokines can facilitate the infiltration of immune cells into the tumor and are often pro-tumor in nature. As the tumor-immune microenvironment (TIME) is infiltrated with myeloid cells and lymphocytes along with the acellular stroma, it can form a supportive bionetwork that could promote primary tumor growth and prepare and establish a premetastatic niche at distant sites for colonization of circulating tumor cells from the blood and lymphatic system. Also, TIME can facilitate colonization and growth of DTCs at the predilection sites such as the lungs, bones, and the brain. Antagonizing the chemokine network can alter the TIME, allowing one to control the colonization and establishment of the metastatic seed. The overall goal is to improve the quality of life and prolong the lives of patients with metastatic TNBC.