However, only one study reported on neoadjuvant resected NSCLC with a small cohort size of 20 patients, of which only five were squamous NSCLC. Instead of using conventional chemotherapy pathologic response criteria (cPRC), immune-related pathologic response criteria (irPRC) were recently proposed to assess the pathologic features of response to neoadjuvant immunotherapy in resection specimens, showing improved performance compared with cPRC 13. Unlike the direct killing effects of chemotherapy by cell toxicity, neoadjuvant immunotherapy has a distinct mechanism of indirect tumor eradication by activating tumor-specific T cells, which may lead to different pathologic changes in the anti-PD-1/L1 immune response. This antibody has been tested for safety and activity in patients with advanced solid tumors 10 and approved in China for lymphoma by the Chinese Center for Drug Evaluation in 2018.Įvaluation of pathologic responses after neoadjuvant chemotherapy has been shown to be a good early surrogate to assess treatment effect and predict survival 11, 12. Preliminary pilot studies have shown good efficacy with low adverse effects in NSCLC patients with neoadjuvant anti-PD-1 immunotherapies 8, 9, including sintilimab, which is a recombinant humanized anti-PD-1 mAb that blocks interactions between PD-1 and its ligands. It has been hypothesized that neoadjuvant immunotherapy for early stage NSCLC has the advantage of maximizing T-cell activation using the primary tumor as an antigen source, as well as systemic elimination of micro-metastases, which are the source of postsurgical relapse. In addition to targeted therapy, recent success with immunotherapies that block the immune inhibition of programmed death 1 (PD-1) protein or its ligand PD-L1 in different tumor types has brought major advances for the treatment of advanced NSCLC 4, 5, 6, 7, including squamous NSCLC. The two major histological types of NSCLC are adenocarcinoma and squamous NSCLC, which constitute ~40 and 25–30% of lung cancers, respectively 1, 2, 3.

Non-small-cell lung cancer (NSCLC) accounts for ~85% of all newly diagnosed lung cancers. These findings demonstrated that assessment of pathologic responses in both primary tumor and LNs may be important as a surrogate for assessing neoadjuvant immunotherapeutic efficacy. Residual viable tumor (RVT) cells in 8/9 MPR specimens had 100% immune-activated phenotype, while a median of 80% of RVT cells in pathologic nonresponse specimens presented immune-excluded/desert phenotype. pCR was achieved in 6/19 N1 nodes and 1/7 N2 nodes. Among 20 patients with pathologically identified tumor beds in lymph nodes (LNs), 10 and six patients achieved pCR/MPR in primary tumors and paired LNs, respectively. Among them, seven (46.7%) were assessed as radiological partial response and eight (53.3%) as stable disease. Fifteen (48.4%) patients achieved pathologic complete response (pCR) or major pathologic response (MPR). We analyzed pathologic responses in surgical specimens obtained from 31 squamous non-small cell lung cancer (NSCLC) patients receiving neoadjuvant anti-PD-1 treatment.

Neoadjuvant immunotherapy provides a unique opportunity for understanding therapeutic responses.

Pathological complete response