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Background <p>Neoadjuvant immunochemotherapy (nICT) has reshaped the treatment paradigm for locally advanced esophageal cancer (EC), but patient responses remain highly heterogeneous. Reliable biomarkers to predict therapeutic benefit are urgently needed. Class I human leukocyte antigen (HLA-I) molecules are essential for anti-tumor immunity, presenting neoantigens to cytotoxic T lymphocytes.This study investigated the relationship between germline HLA-I genotypes and treatment response in patients with esophageal cancer receiving nICT.</p> Methods <p>We retrospectively analyzed 30 Chinese EC patients who underwent surgery following nICT. High-resolution sequencing was used to determine germline HLA-I genotypes. Associations between specific HLA alleles and both short-term pathologic response and long-term survival outcomes, including pathologic complete response (pCR) and event-free survival (EFS) were evaluated.</p> Results <p>HLA-A*11:01 carriers exhibited significantly prolonged EFS compared with non-carriers (<i>P</i> = 0.015). In contrast, the HLA-A*24:02 allele was more frequent in non-pCR patients (50.0% vs. 12.5%, <i>P</i> = 0.064), and shorter EFS was observed among carriers (median 16.0 vs. 38.8 months, <i>P</i> = 0.063), although these differences did not reach statistical significance. HLA-I homozygosity was more common among patients who achieved pCR (75.0% vs. 27.3%, <i>P</i> = 0.034).</p> Conclusion <p>In this small retrospective cohort, germline HLA-I genotypes were associated with differences in pathologic response and event-free survival following nICT. These findings should be interpreted as exploratory and hypothesis-generating, requiring validation in larger prospective studies before clinical translation.</p>

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Germline HLA-I genotypes predict pathologic response and survival outcomes in esophageal cancer patients undergoing neoadjuvant immunochemotherapy: a retrospective cohort study

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年5月6日

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  • Willis Wasonga Omindo,
  • Qi Wang,
  • Siyou Deng,
  • Ruijie Zhang,
  • Wei Sun,
  • Li Zhang,
  • Ni Zhang

摘要

Background

Neoadjuvant immunochemotherapy (nICT) has reshaped the treatment paradigm for locally advanced esophageal cancer (EC), but patient responses remain highly heterogeneous. Reliable biomarkers to predict therapeutic benefit are urgently needed. Class I human leukocyte antigen (HLA-I) molecules are essential for anti-tumor immunity, presenting neoantigens to cytotoxic T lymphocytes.This study investigated the relationship between germline HLA-I genotypes and treatment response in patients with esophageal cancer receiving nICT.

Methods

We retrospectively analyzed 30 Chinese EC patients who underwent surgery following nICT. High-resolution sequencing was used to determine germline HLA-I genotypes. Associations between specific HLA alleles and both short-term pathologic response and long-term survival outcomes, including pathologic complete response (pCR) and event-free survival (EFS) were evaluated.

Results

HLA-A*11:01 carriers exhibited significantly prolonged EFS compared with non-carriers (P = 0.015). In contrast, the HLA-A*24:02 allele was more frequent in non-pCR patients (50.0% vs. 12.5%, P = 0.064), and shorter EFS was observed among carriers (median 16.0 vs. 38.8 months, P = 0.063), although these differences did not reach statistical significance. HLA-I homozygosity was more common among patients who achieved pCR (75.0% vs. 27.3%, P = 0.034).

Conclusion

In this small retrospective cohort, germline HLA-I genotypes were associated with differences in pathologic response and event-free survival following nICT. These findings should be interpreted as exploratory and hypothesis-generating, requiring validation in larger prospective studies before clinical translation.