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Tumor stroma ratio, tumor stroma maturity, tumor-infiltrating immune cells in relation to prognosis, and neoadjuvant therapy response in esophagogastric junction adenocarcinoma

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Abstract

Accurate predictions on prognosis and neoadjuvant therapy response are crucial for esophagogastric junction adenocarcinoma (EGJA) patients. Therefore, we aimed to investigate the predictive abilities of several indicators, including tumor stroma ratio (TSR), tumor stroma maturity (TSM), and the density and spatial distribution of tumor-infiltrating immune cells (TIICs), such as T cells, B cells, and tumor-associated macrophages (TAMs). Resection and biopsy specimens of a total of 695 patients were included, obtained from the National Cancer Center (NCC) and The Cancer Genome Atlas (TCGA) cohorts. TSR and TSM were evaluated based on histological assessment. TIICs were quantified by QuPath following immunohistochemical (IHC) staining in resection specimens, while the Klintrup–Mäkinen (KM) grade was employed for evaluating TIIC in biopsy specimens. Patients with high stromal levels or immature stroma had relatively worse prognoses. Furthermore, high CD8+T cell count in the tumor periphery, as well as low CD68+ TAM count either in the tumor center or in the tumor periphery, was an independent favorable prognostic factor. Significantly, the combination model incorporating TSM and CD163+TAMs emerged as an independent prognostic factor in both two independent cohorts (HR 3.644, 95% CI 1.341–9.900, p = 0.011 and HR 1.891, 95% CI 1.195–2.99, p = 0.006, respectively). Additionally, high stromal levels in preoperative biopsies correlated with poor neoadjuvant therapy response (p < 0.05). In conclusion, our findings suggest that TSR, TSM, CD8+T cell, CD68+TAMs, and CD163+TAMs predict the prognosis to some extent in patients with EGJA. Notably, the combined model incorporating TSM and CD163+TAM can contribute significantly to prognostic stratification. Additionally, high stromal levels evaluated in preoperative biopsy specimens correlated with poor neoadjuvant therapy response.

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Data availability

1. The datasets used and/or analyzed in our cohort are available from the corresponding author on reasonable request.

2. The datasets used in our study from TCGA cohort are available in TCGA-STAD cohort (https://portal.gdc.cancer.gov/projects/TCGA-STAD).

Abbreviations

CAFs:

Cancer-associated fibroblasts

CPS:

Combined positive score

EGJA:

Esophagogastric junction adenocarcinoma

GMS:

Glasgow microenvironment score

HE:

Hematoxylin and eosin

IHC:

Immunohistochemical

MPR:

Major pathological response

pCR:

Pathologic complete regression

TAMs:

Tumor-associated macrophages

TCGA:

The Cancer Genome Atlas

TIICs:

Tumor-infiltrating immune cells

TME:

Tumor microenvironment

TRG:

Tumor regression grade

TSR:

Tumor stroma ratio

TSM:

Tumor stroma maturity

Tc:

Tumor center

Tp:

Tumor periphery

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Acknowledgements

The authors would like to thank Bingning Wang, Hua Zeng, and Wenchao Liu for their assistance in the immunohistochemical staining involved in the current study.

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Authors and Affiliations

  1. Department of Pathology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 17 Panjiayuan, Chaoyang District, Beijing, 100021, China

    Na Cheng, Bingzhi Wang, Jiaqi Xu, Liyan Xue & Jianming Ying

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  1. Na Cheng
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Contributions

J.Y. and L.X. provide guidance and revise manuscripts. N.C. contributed to the methodology, data analysis, and writing; B.W. provided acquisition, analysis, and interpretation of data. J.X. contributed to the clinicopathological data acquisition. All authors read and approved the final paper.

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Correspondence to Liyan Xue or Jianming Ying.

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Ethics approval and consent to participate

The study was approved by the Institutional Review Board of National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, and individual consent was waived for this retrospective analysis.

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Informed consent was obtained from all individual participants included in the study.

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Cheng, N., Wang, B., Xu, J. et al. Tumor stroma ratio, tumor stroma maturity, tumor-infiltrating immune cells in relation to prognosis, and neoadjuvant therapy response in esophagogastric junction adenocarcinoma. Virchows Arch (2024). https://doi.org/10.1007/s00428-024-03755-2

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