Camrelizumab and Chemotherapy as Neoadjuvant Treatment for Locallyadvanced Esophageal Squamous Cell Carcinoma (Escc)a Single-Arm, Phase Ii Trial

Abstract Background This study (NCT05476380) aimed to evaluate the safety and efficacy of neoadjuvant camrelizumab plus chemotherapy in patients with locally advanced ESCC, and to explore the potential risk factors of tumor immune microenvironment (TIM) which affect the efficiency of immunotherapy. Methods Patients with resectable ESCC, staged as T1b-4a, N2–3 (≥ 3 stations), and M0 or M1 lymph node metastasis were enrolled. Eligible patients received intravenous camrelizumab (200 mg, day 2) plus paclitaxel (175 mg/m2, day 1) and cisplatin (75 mg/m2, day 1) for three 21-day cycles before surgery. The primary endpoint was major pathological response (MPR), defined as ≤10% residual viable tumor cells in resected tissue. In order to screen out the biomarkers, the dissected lymph nodes were collected in the pathological complete response (pCR) and non-pCR groups. The infiltrated immune cells and the status of PD-L1 was evaluated. Results 38 patients were enrolled. 34 (89.5%) patients completed the full three-cycle treatment successfully. MPR: 67.6% (23/34), pCR: 17.6% (6/34). Compared with MPR group, the infiltrated lymphocyte cells in the non-MPR group decreased from 93% to 52.4% (p = 0.02), the infiltrated CD8+ T cells also decreased from 11.8% to 5.9% (p = 0.02). The CD4+ T cells showed no significant difference between the two groups. The expression of PD-L1 in the CD8+ T cells showed significant difference between the MPR and non-MPR groups (14.5% vs 6.7%, p = 0.02). More infiltrations of MDSCs in the non-MPR group compared with the MPR group (9.7% vs 4.7%, p = 0.04). Conclusion Neoadjuvant camrelizumab combined with chemotherapy shows promising efficacy and good safety in ESCC patients. Poor response to immunotherapy was related to lymph node metastasis in the TIM. Myeloid-derived suppressor cells (MDSCs) are a group of vastly heterogeneous immunosuppressive cells derived from immature myeloid progenitors that have been linked to poor patient prognosis and immunosuppression.