Unravelling the Difference of Immune Microenvironment Characteristics between Esophageal Basaloid Squamous Cell Carcinoma and Conventional Esophageal Squamous Cell Carcinoma.

Objectives: Esophageal basaloid squamous cell carcinoma (basaloid ESCC) is an uncommon variant of esophageal squamous cell carcinoma (ESCC). We characterized the tumor immune microenvironment features of basaloid ESCC, and compared them with conventional ESCC.

Methods And Results: One hundred and four basaloid ESCC patients and 55 conventional ESCC patients were included in Cohort 1. Among 104 basaloid ESCC, 81 were pure basaloid ESCC, and 23 were mixed basaloid ESCC with invasive basaloid ESCC components and ESCC components. In pure basaloid ESCC, there were more immature desmoplastic reaction (P<0.001), fewer peritumoral tertiary lymphoid structures (TLSs) (P<0.001), and lower tumor proportional score (TPS) and combined positive score (CPS) (P<0.001 and P=0.004) than in conventional ESCC. In mixed basaloid ESCC, the number of mature or intermediate desmoplastic reaction (P<0.001), the tumor-infiltrating lymphocytes (TILs) score (P=0.043), the proportion of stromal CD8 TILs (P=0.047), the number of intratumoral CD20 TILs (P<0.001), the number of peritumoral TLSs (P=0.001), the number of peritumoral matureTLSs (P=0.021), and the PD-L1 (22C3) CPS (P=0.016) were lower in the basaloid ESCC components than in the conventional ESCC components. In addition, the data of 141 ESCC patients with neoadjuvant chemoimmunotherapy (nICT) were collected to compare immunotherapeutic outcomes. Among 141 nICT-treated patients, 115 patients had residual tumor cells remaining, including 101 with conventional ESCC and 11 with basaloid ESCC. In basaloid ESCC, 18.2% patients had less than 10% residual viable tumor in the esophageal wall (effective response), which was lower than 58.6% in conventional ESCC (P=0.025).

Conclusions: Our data indicated that basaloid ESCC had less benefits from immunotherapy than conventional ESCC, and manifested as immune "cold" with immature-type desmoplastic reaction, lower TILs, lower peritumoral TLSs, and lower PD-L1 expression than conventional ESCC.