ArticleFrontiers in immunology2026
Acquired resistance to first-line immune checkpoint inhibitors in esophageal squamous cell carcinoma: progression patterns and prognostic implications.
Article in Frontiers in immunology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Background: Despite the survival benefit of first-line immune checkpoint inhibitor (ICI)-based therapy in advanced esophageal squamous cell carcinoma (ESCC), acquired resistance (AR) remains a major clinical challenge, and its progression patterns and prognostic significance are poorly defined. This study aimed to characterize progression patterns and sites at AR after first-line ICI-based therapy in ESCC and to evaluate their associations with clinical outcomes. Methods: We retrospectively identified patients with metastatic or unresectable locally advanced ESCC who underwent first-line ICI-based therapy at the First Affiliated Hospital of Zhengzhou University and Anyang Cancer Hospital (September 2023-January 2026). Initial clinical benefit was defined as complete response, partial response, or stable disease lasting ≥6 months; AR was defined as subsequent disease progression or death. Progression was classified as oligoprogression (≤2 sites) or polymetastatic progression (≥3 sites). Overall survival (OS) was estimated using the Kaplan-Meier method and analyzed with Cox models. Results: Among 1,537 patients treated with ICIs, 106 patients with ESCC who developed AR were included. Oligoprogression was the most common AR pattern (85/106, 80.2%), whereas 21 (19.8%) had polymetastatic progression. Polymetastatic progression was associated with worse OS than oligoprogression (HR = 1.97, 95% CI 1.12-3.47; p = 0.016). Conclusions: Oligoprogression was the dominant pattern of AR, and lymph nodes were the most frequent progression sites. Polymetastatic progression was associated with poorer OS.
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