PD-L1 expression is found in a variety of solid tumors, such as melanoma, lung cancer, thymoma, ovarian cancer, renal cell carcinoma, esophageal squamous cell carcinoma, colorectal, prostate, and bladder cancer, and the expression of the PD-L1 gene is directly related to the growth of cancer cells [11, 15, 16]. The expression of PD-L1 in breast cancer varies according to its subtypes. According to studies by Gebbeh et al., the PD-L1 gene is expressed in about 50% of breast cancers [17]. TNBCs have the highest expression among breast cancer subtypes, followed by HER2 overexpression subtypes [18]. Finally, luminal A and B subgroups are associated with the lowest expression that has little effect on the prognosis of patients and the reduction in survival [10, 19]. The present study measured the expression of PD-L1 gene expression in MDA-231, MDA-468, SK-BR-3 cell lines, which represents TNBC subtypes for MDA-231,468 and HER2 overexpression for SK -BR-3 and comparing its results with PD-L1 gene expression in these categories after the addition of common chemotherapy drugs.
In previous studies, it is proven that the expression of PD-L1 increases in different breast cancer cell lines and other cancers such as lung cancer, prostate cancer, and esophageal cancer. In the present study, the increase in PD-L1 gene expression in the studied cell lines related to triple-negative and basal-like breast cancer was calculated, which is consistent with these studies. A study by Bailey C, et al. shows that chemotherapy drugs such as Doxorubicin, Etoposide, Busulfan, and others can increase PD-L1 gene expression, which is consistent with the results of our study [20]. Another study by Yang et al. on stromal tuberculosis cancer cell lines of the bone marrow showed that the expression level of PD-L1 cells in stromal tuberculosis cells was low before the addition of drugs [21]. Common chemotherapy drugs used in these cancers, including Doxorubin, Cytarabine, Oxaliplatin, Vincristine, and Etoposide, increase the expression of PD-L1 in these cells, which is consistent with the effect of Doxorubicin in the present study. In another study by Yan Hoy et al. PD-L1 gene expression was measured in esophageal squamous cell carcinoma cell lines under the influence of Paclitaxel and Carboplatin and 5-Fluorouracil plus Cisplatin which was found to be associated with an increase in PD-L1 gene expression [16]. This finding is consistent with the results of the present study on the increased expression of the PD-L1 gene under the influence of Paclitaxel. In a study by Zhang P. et al., the expression of PD-L1 protein expression in cell lines MDA-MB-468, MDA-MB-435, MCF-7 with Paclitaxel, and Etoposide and 5-Fluorouracil was performed by flow cytometry of cell surface proteins, which resulted in increased gene expression in all three cell lines [22]. The results of the effect of paclitaxel on the MDA-MB-468 cell line are similar to the present study. In a study by Funaki et al., the expression of genes in lung cancer cell lines and human living tissue samples under the influence of Paclitaxel and Cisplatin were examined, which resulted in increased expression of the PD-L1 gene which was in line with the results of our study [23]. In a study by Zili et al., the effect of monoclonal antibodies against PD-L1 along with Docetaxel on melanoma cell lines was studied, which resulted in a positive and enhanced effect of these drugs on their use [24]. It alone can induce the inhibition of PD-L1 protein by antibodies and enhance the effect of Docetaxel. However, no separate study was found on the effect of Docetaxel on different cell lines, which remains to be another study to evaluate the effects of this drug on PD-L1 expression.
Chemotherapy for cancer is divided into three types. After surgery or adjuvant treatment for breast cancer, which is used to treat micrometastatic diseases (i.e., breast cancer cells that have escaped from the breast and lymph nodes in the area but have not yet been identified as a metastasis). Despite surgical treatment, there is an increased risk of recurrence of cancer, so adjuvant therapy reduces the risk of recurrence and death from breast cancer. The next type is neoadjuvant therapy, which is used before surgery for newly diagnosed cancers whose tumor size is too large to be surgically removed. In these cases, the tumor is first reduced in size by chemotherapy and then surgery is performed. The tumor response to chemotherapy drugs can also be measured and used after surgery if needed. And like adjuvant therapy, it reduces the chance of recurrence [25]. Depending on the risk reduction model, breast cancer adjuvant and neoadjuvant therapy including PD-L1-based therapies may provide an efficient therapeutic strategy for breast cancer therapy [26].