Discussion
cancer, tumor, TCGA, tumors
TUMOR, ADVERSE EVENTS, CANCER, CPS, TUMORS
Neoadjuvant PD-L1 blockade was well tolerated with a lower incidence of treatment-related adverse events compared with standard-of-care chemotherapy/chemoradiotherapy in resectable ESCC, consistent with observations in lung cancerConsidering the tumor response, despite small studies of nCTA key result of the exploratory biomarker was the first-defined classification of a TME phenotype to stratify all MPR patients in response to neoadjuvant PD-L1 blockade, as well as patients with longer OS in the TCGA ESCC and nine pan-cancer immunotherapy cohorts. We classified all patients into IE, tumor-proliferation and fibroblast-enriched subtypes according to unique compositions of immune cells and stromal cells, along with the pathway activity of cancer hallmarks. Importantly, the IE subtype was correlated with the pathological response to neoadjuvant anti-PD-L1 blockade. The benefit of nAde was limited to IE tumors at baseline, most notably tumors with high PD-L1 expression (combined positive score (CPS) > 10). This finding is in line with Chen et al.Blockade of the PD-1–PD-L1 axis was thought to primarily boost pre-existing tumor-specific T cell responses. We demonstrated that the clonotype diversity of pre-existing ITCs most likely to recognize tumor neoantigens was associated with favorable clinical benefits, and the clonotypic dynamics of pre-existing ITCs were hallmarks of responsive patients. Neoadjuvant adebrelimab induced clonal replacement of pre-existing T clones and new emergent T clonotypes, which was consistent with published results in the context of anti-PD-1 therapyOur study is limited by its small sample size and single-center nonrandomized setup. Comparing patients in trials with real-world patients has several challenges owing to various factors, including differences in the study duration and the availability of other therapies during different periods. With a median follow-up of 27 months, further continuous follow-up should be carried out to fully evaluate clinical outcomes. However, this preliminary result is encouraging, and comparison with the previously published CMISG1701 study supports the importance of neoadjuvant PD-L1 blockade as a new therapeutic strategy, especially for patients intolerant of chemotherapy or chemoradiotherapy. An additional larger cohort and well-designed head-to-head comparison with nCRT or nCT that are beyond the scope of this study are planned.These data are complementary to standard-of-care treatments in neoadjuvant settings. The translational study identified patients with favorable pathological responses to immunotherapy, supporting a promising alternative regimen to avoid overtreatment by chemotherapy and chemoradiotherapy with or without immunotherapy.