Do the characteristics of the immune microenvironment of patients with 11q13 gene amplification reveal that it is an important factor for immune hyperprogression?

Abstract

e16069 Background: Amplification of the 11q13 chromosomal region, encompassing genes such as CCND1 and FGF3/4/19, is frequently observed in esophageal cancer and has been implicated in tumor progression. However, the prevalence of 11q13 amplification far exceeds the incidence of hyperprogressive disease (HPD), raising uncertainty about its predictive value. This study aimed to characterize the immune microenvironment associated with 11q13 alterations in esophageal cancer and to explore their potential relevance to HPD. Methods: A total of 114 Chinese patients with esophageal cancer were enrolled. Genomic alterations were identified using next-generation sequencing (NGS). The immune landscape of both tumor parenchyma and stroma was profiled using multiplex immunohistochemistry (mIHC) and APTime pathology analysis software, quantifying multiple immune cell populations. Results: Patients were stratified based on 11q13 alteration status into a variant group (n = 36) and a non-variant group (n = 78). The variant group was predominantly characterized by copy number amplifications (94.4%), with only two cases harboring single-nucleotide variants. Consistent with previous reports, the non-variant group exhibited a high prevalence of TP53 mutations (63/78, 80.8%). Comparative immune profiling revealed significantly higher infiltration of M2 macrophages in the tumor parenchyma of the variant group compared with the non-variant group (P = 0.0301). In addition, both parenchymal and stromal levels of CD56 + dim NK cells (P = 0.0047 and P = 0.0416, respectively) and CD56 + bright NK cells (P = 0.0238 and P = 0.0406, respectively) were significantly increased in tumors harboring 11q13 alterations. No significant differences were observed between groups in adaptive immune components, including T cells, B cells, and PD-L1 expression. Conclusions: 11q13 alterations are associated with distinct innate immune microenvironment features in esophageal cancer, including M2 macrophage enrichment and increased NK cell infiltration, but not with adaptive immune markers. These findings suggest that 11q13 alterations may influence tumor biology through modulation of innate immunity rather than serving as direct drivers of HPD. Further studies incorporating treatment response and clinical outcome data are warranted to clarify the prognostic and predictive significance of 11q13 alterations.