Response to neoadjuvant immune checkpoint inhibitors and chemotherapy in Chinese patients with esophageal squamous cell carcinoma: the role of tumor immune microenvironment

Abstract

Background: Immune checkpoint inhibitors (ICIs) through programmed cell death 1 blockade improve the survival outcomes of patients with advanced esophageal squamous cell carcinoma (ESCC). Recently, the use of neoadjuvant immunotherapy for the treatment of ESCC has been gradually increasing. We aimed to evaluate the efficacy of neoadjuvant treatment of ICIs with chemotherapy and explore tumor microenvironment (TME) immune profiles of ESCC samples during neoadjuvant therapy.

Methods: Patients with previously untreated, resectable, locally advanced ESCC (stage II or III) in Harbin Medical University Cancer Hospital were enrolled. Each patient received two to four cycles of neoadjuvant ICIs combined with chemotherapy before surgical resection. The TME immune profiles of formalin-fixed paraffin-embedded tumor samples at baseline and after surgery were evaluated by multiplex staining and multispectral imaging.

Results: In all, 18 patients were enrolled, and all patients received surgery with R0 resection. The postoperative pathological evaluation indicated that 7 (38.9%) patients had a pathological complete response (pCR) and 11 (61.1%) patients had a partial response. The neoadjuvant therapeutic regimens had acceptable side effect profiles. The TME immune profiles at baseline observed higher densities of stroma CD3 + , PD-1 + , and PD-1 + CD3 + cells in pCR patients than in non-pCR patients. Comparing TME immune profiles before and after neoadjuvant treatment, an increase in CD8 + T cells and a decrease in CD163 + CD68 + M2-like macrophage cells were observed after neoadjuvant treatment.

Conclusions: Neoadjuvant ICIs combined with chemotherapy produced a satisfactory treatment response, demonstrating its anti-tumor efficacy in locally advanced ESCC. Further large-scale studies are required to understand the role of tumor immunities and ICIs underlying ESCC.

Keywords: Combination; Esophageal squamous cell carcinoma (ESCC); Immune; Immunotherapy; Neoadjuvant; Tumor microenvironment (TME).