Pulmonary carcinomas have developed several mechanisms to evade immune cell attack. Among these mechanisms, the programmed death 1 (PD-1), programmed death ligand 1 and 2 (PD-L1/2), and the cytotoxic T-lymphocyte-associated protein 4 system have garnered particular interest. Tumor cells and lymphocytes express ligands for PD-1, which induce apoptosis or exhaustion of CD8 T cells. This further impacts the microenvironment (MEV) composed of cytokines, leading to immune tolerance. Therapies targeting PD-L1 expression have shown significant success in restoring the function of T-lymphocytes against tumor cells. Antibodies against the PD-1 receptor have been developed and tested in clinical trials with positive outcomes. Immunohistochemistry tests for PD-1 and PD-L1 expression are used to select patients likely to respond to this therapy. A strong PD-L1 staining in at least 1% of tumor cells and/or lymphocytes (or 50% in one trial) was considered a positive result and was associated with patient prognosis. This criterion was used to determine eligibility for anti-PD-L1 therapy. However, PD-L1 expression thresholds vary across clinical trials and therapeutic agents, with some drugs requiring PD-L1 positivity in ≥50% of tumor cells. Based on data from previous clinical trials, most patients were diagnosed using this simple staining method. However, false-positive and false-negative results have been reported in some patients. Resistance and immune escape mechanisms of pulmonary carcinoma have been extensively investigated. Some of these mechanisms involve the metabolic reprogramming of tumor cells within the tumor MEV. Several immune checkpoint molecules have been identified and further tested. In addition, the composition of the tumor stroma, including various types of lymphocytes and dendritic cells, has gained considerable attention.

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