Abstract
In addition to surgery, chemotherapy, radiotherapy, and targeted therapy, immunotherapy has emerged as a standard pillar of cancer treatment. Immune checkpoint inhibitors (ICIs) such as targeting programmed death-1/programmed death ligand 1 (PD-1/PD-L1) and cytotoxic T lymphocyte antigen 4 (CTLA-4) have been integrated into standard-of-care regimens for patients with advanced lung squamous cell carcinoma (LUSC), who were previously limited by the lack of treatment options. Atezolizumab, durvalumab, nivolumab, and pembrolizumab are all currently used as part of standard-of-care treatment for different stages of lung cancer. Recent successes and failures of immune checkpoint blockade-based combination therapies have provided significant insights into implementing combination strategies in LUSC. Therefore, there is an urgent need to correctly select patients who are more likely to respond to immunotherapy and understand the mechanisms of primary or acquired resistance. In this review, we aim at summarizing the emerging clinical data on the promise and challenge of ICIs, discussing the unmet need of potential biomarkers for predicting response or resistance to immunotherapy, and providing an overview of the current immune landscape and future directions in advanced LUSC.
Highlights
For those patients who may not tolerate chemotherapy and have programmed death ligand 1 (PD-L1) expression (TPS > 1%), single-agent pembrolizumab may be taken into consideration based on KeyNote-042 [20], the benefit of this approach was largely driven by patients with high expression of PD-L1
In-depth tumor analysis including whole-genome sequencing, single cell RNA-sequencing, multidimensional flow cytometry, or epigenetics might be implemented in the future in order to find individualized treatment strategies
Consideration of common properties across squamous cell carcinoma (SCC) as they relate to epigenetics, genomics, genetics, and transcriptomes may serve as a foundation for individual and combinatorial therapeutics, as well as understanding the mechanistic basis of treatment resistance
Summary
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. PD-L1 TPS ≥ 50%, without a sensitizing EGFR mutation or ALK translocation; Approved for treatment of locally advanced or metastatic NSCLC patients with PD-L1 TPS ≥ 1%, and disease progression during/after first-line chemotherapy. Immunotherapy is widely used in the care of patients with NSCLC, and multiple standard-of-care (SOC) regimens are approved in metastatic LUSC (Table 2) Studies such as KeyNote-010 [11], CheckMate 017 [12,13,14] /078 [15], POPLAR [16], and OAK [17,18] have proven that ICIs can improve the prognosis of patients with advanced NSCLC, bringing about a new alternative for second-line treatment. The incidence of severe or life-threatening adverse events (grade 3 or higher) ranged from 7% to 15% with ICIs versus 35% to 55% as compared with docetaxel
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