Neoadjuvant PD-1 Inhibitor combines with Chemotherapy in Resectable Squamous Cell Non-Small Cell Lung Cancer

Background Single agent of PD-1 or PD-L1 inhibitor has been explored recently for resectable patients before surgery. However, the effectiveness and safety of neoadjuvant PD-1 blockade combine with platinum-based doublet chemotherapy has not been fully investigated. Methods 21 patients with squamous cell lung cancer accepted neoadjuvant therapy followed by surgery in Beijing Cancer Hospital were involved. 8 patients accepted two cycles of neoadjuvant platinum-based doublet chemotherapy combine with anti-PD-1 therapy, while 13 patients accepted two cycles of neoadjuvant platinum doublet chemotherapy. Besides baseline tumor staging, chest CT was repeated two to three weeks before surgery. Adverse events were monitored. Peripheral lymphocytes counting was tested during whole treatment. The residual viable tumor cells were counted after surgery to decide a major pathological response (MPR) rate. Selected specimen was sent for immunohistochemical, multiplex immunofluorescence analyses, and T-cell receptor DNA sequencing. Results Comparing with neoadjuvant chemotherapy alone, combination with PD-1 blockade and chemotherapy increased the pathological complete response rate (37·5% Vs. 7·69%) and MPR rate (50% Vs. 38·46%). The pathological evaluation is not consistent with that of radiological evaluation. Although peripheral lymphocyte counting was influenced by neoadjuvant therapy, no unknown adverse effects were reported for all the patients. The tumor infiltrating lymphocytes were observed more in patients accepted PD-1 blockade, and seem infiltrated more in relative “non-responders”. No special pathological features associated with PD-1 blockade were found. Multiplexed immunofluorescence analyses revealed potential immune suppression status in the peritumoral spaces around the residual tumor cells. T-cell receptor DNA sequencing found although some amino acids were shared in primary tumor and lymph nodes in single patients, they are hardly shared among different patients. Conclusions Neoadjuvant chemotherapy combine with PD-1 blockade is safe and feasible for patients with potentially resectable squamous cell lung cancer, to improve the clinical and pathological outcome. Even with PD-1 blockade, the immune suppressive status around the residual tumor cells still exists. The squamous cell lung cancers, and corresponding immune responses are extremely highly individualized. The treatment needs to be designed accordingly. The combination strategy of traditional neoadjuvant chemotherapy with current anti-PD-1 inhibitor are still need further investigation.