Parnad Basu, Amity University Kolkata
Breast cancer is the second most common cancer in the United States, which happens to women but is also seen in men in some rare cases. Now, triple-negative breast cancer (TNBC) is a specific type of breast cancer where the cancer cells show negative results for estrogen receptor, progesterone receptor, and HER-2 (human epidermal growth factor receptor 2) protein. TNBC grows and spreads faster and also has very limited treatment options. Normally, BRCA (breast cancer gene)-associated breast cancer is treated using PARP (poly (ADP-ribose) polymerase) inhibitors. However, in recent medical trials immunotherapy is being used along with PARP inhibitor therapy.
Although, scientists are thinking of going ahead of it by identifying different ways to boost the response to PARP inhibitors. While doing that, scientists have found a weak spot in PARP inhibition treatment, macrophage-mediated immune suppression. It was found that macrophages are working to limit the T cell’s activation ability in the tumor microenvironment as macrophages become highly suppressive after PARP inhibitor therapy. PARP inhibitors recruit T cells to recognize the presence of cancer cells. Macrophages are a type of immune cell, and they repair and strengthen the tumor state. But, if CSF-1R-positive macrophages can be targeted with PARP inhibition may lead to an enhanced anti-tumor response.
A study was done in mice having BRCA-deficient TNBC. Astonishingly, a combination of PARP inhibitor, CSF-1R inhibitor, and SREBP1 (lipid metabolism regulator) was able to neutralize tumors in the case of those mice. From that, it can be inferred that PARP inhibitors directly activated macrophages to be suppressive in the tumor microenvironment. Scientists are even doing biopsies after the treatment begins to understand these mechanisms. Further research on this can prove this technique very fruitful in BRCA-deficient breast cancer along with many other possible applications.
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Reference: Targeting immunosuppressive macrophages overcomes PARP inhibitor resistance in BRCA1-associated triple-negative breast cancer Jennifer L. Guerriero et al. https://doi.org/10.1038/s43018-020-00148-7
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