One of the most common cancers worldwide is cancer of lung, with the highest mortality among cancers [1]. In 2019, 228,150 cases of lung cancer and 142,670 cancer-related diseases were reported in the United States of America, being responsible for about 24% of all cancer deaths in the country [2]. Histologically, lung cancer is categorized into two key groups, small cell lung cancer cell and non-small cell lung cancer. Non-small cell lung cancer (NSCLC) accounts for nearly 85% of all lung cancer cases [3]. Smoking is a main risk factor for this cancer which includes about 80–90% of patients suffering from lung cancer. Nonsmoker individuals are 20 times less probable to develop lung cancer than those who continue to smoke [4]. In addition, exposure to arsenic, asbestos, chromium, nickel, and radiation exposure comprising radon in households and mines, alcohol consumption, exposure to air pollution, chronic inflammation due to infection or other chronic disease also increase the risk of lung cancer [5, 6].
The treatment is chosen based on the histological and molecular type and stage of cancer. Surgery is currently the only viable and successful treatment option. Surgical resection is the preferred method for T1b and larger tumors [7]. However, 70% of patients bearing lung cancer have local invasion or metastasis at the time of diagnosis, who do not have the obligatory condition for surgery. Other treatment methods include chemotherapy alongside radiation for some locally advanced cancers, palliative chemotherapy and palliative radiation, and target therapy combined with chemotherapy for metastatic disease [7, 8]. Platinum-based chemotherapy is extensively acknowledged as the standard therapeutic strategy. Common chemotherapy regimens are: cisplatin and paclitaxel, cisplatin and gemcitabine, cisplatin plus docetaxel and carboplatin plus paclitaxel [5, 9, 10].
The average survival of patients bearing metastatic untreated cancer is only 4 to 5 months, and the one-year survival rate is only 10%. Cancer patients' overall survival has not enhanced significantly despite significant advances in cancer treatment using conventional techniques like chemotherapy, radiotherapy, and surgery over the past decade. The 5-year survival of patients’ post-treatment remains only 17.4% [11, 12]. Among these methods, chemotherapy is widely used to hinder the cancer cells’ growth of and apoptosis induction in them. Although chemotherapy does not directly kill immune cells due to cytotoxicity, it inhibits the immune response against tumor. So, resistance of cancerous cells to the immune system and immune evasion are major limitations of chemotherapy. During the last few years, as a complementary strategy, immunotherapy can be useful in eradicating cancer cells in combination with traditional chemotherapy [13, 14].
Immune checkpoints are regulators of the immune system that keep tissues from harm when the immune system responds to a pathogenic infection. These molecules are essential to maintain balance and autoimmunity prevention [15]. The expression of immune checkpoints proteins by tumor cells is an essential mechanism of tumor resistance to the immune system, which causes the immune system to escape and an insufficient anti-tumor response[16]. PD-L1 (Programmed Death Ligand 1), as a participant of the CD28 family and a vital immune checkpoint receptor, is expressed on the surface of active T, B, and NK cells and has an important role in tumor escape from the immune system. Besides PD-L1, the major PD-1 ligand is expressed in various tumors, including NSCLC, breast, gastric, colorectal, papillary thyroid, and testicular cancers. PD-L1 which is expressed on tumor cells, binds to PD-1 which is expressed on T cells and inhibits a cytotoxic T-cell response and T-cell–induced anti-tumor activity [17–19]. According to numerous studies, high expression of PD-L1 in lung cancer promotes metastasis and invasion and weakens the prognosis of these patients [11, 20, 21]. Thus, blocking the PD-L1 and PD-1 pathways via PD-1 / PD-L1 blockers results in sustained anti-tumor responses and improves prognosis in many cancers, including lung cancer [17, 19, 22].
The effects of chemotherapy in lung cancer patients on immune response are not yet fully understood. Also, due to the evidence of the influence of amplified the expression of PD-L1 on the lung cancer prognosis and its resistance against the immune system and inhibition of T cells, there is a need to investigate the interactions of common therapies and PD-L1 expression.
Since chemotherapy is still utilized as the initial line of therapy for lung cancer, a deeper comprehension of the impact of chemotherapy agents on immune response against the tumor, especially in immune evasion, is important in improving the effectiveness of immunotherapy and chemotherapy combined. In the current research, particularly, the effects of common chemotherapy drugs used in lung cancer on expression of PD-L1 in tumor cells were investigated in order to help select appropriate treatment regimens to optimize treatment, increase patient survival, observe more improvement, and a better prognosis for lung cancer.