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Immunoscore is a strong predictor of survival in the prognosis of stage II/III gastric cancer patients following 5-FU-based adjuvant chemotherapy

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Abstract

The prognostic impact of Immunoscore (IS) in gastric cancer (GC) patients treated with adjuvant chemotherapy remains unelucidated. We evaluated the CD3 + , CD8 + , and Foxp3 + T-lymphocyte densities in tumor centers and invasive margin regions of 389 patients with surgically resected stage II/III GC who received 5-FU-based adjuvant chemotherapy and investigated the impact of IS on survival. In univariate analysis, high CD3 + , CD8 + , and Foxp3 + T-lymphocyte densities in the invasive margin were correlated with better prognosis (all P < 0.05). Patients with high IS had significantly longer disease-free survival (DFS; P < 0.001) and overall survival (OS; P < 0.001). In multivariate analysis, IS demonstrated a powerful prognostic impact on patient outcome [DFS, hazard ratio (HR) = 0.465; 95% confidence interval (CI), 0.306–0.707, P < 0.001; OS, HR = 0.478; 95% CI, 0.308–0.743, P = 0.001]. Additionally, although all EBV-positive cases had high IS, IS was similar in both microsatellite instability (MSI)-high and microsatellite stable (MSS)/MSI-low groups (83.3% and 80.5%, respectively). Subgroup analysis according to MSI status revealed that high IS patients had significant DFS and OS benefits in both MSS/MSI-low (DFS, HR = 0.527, 95% CI, 0.341–0.816, P = 0.004; OS, HR = 0.528, 95% CI, 0.334–0.837, P = 0.007) and MSI-high (DFS, HR = 0.166, 95% CI, 0.033–0.826, P = 0.028; OS, HR = 0.177, 95% CI, 0.036–0.883, P = 0.035) groups. Thus, the assessment of immune cell infiltration based on IS may provide a strong indicator of survival in stage II/III GC patients with curative resection following 5-FU-based adjuvant chemotherapy.

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Abbreviations

CT:

Center of tumor

DFS:

Disease-free survival

EBV:

Epstein–Barr virus

GC:

Gastric cancer

HER2:

Human epidermal growth factor receptor 2

IM:

Invasive margin

IS:

Immunoscore

MSI:

Microsatellite instability

MSS:

Microsatellite stable

OS:

Overall survival

PCR:

Polymerase chain reaction

PDL1:

Programmed cell death ligand 1

TIL:

Tumor infiltrating lymphocyte

Treg:

Regulatory T cell

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Funding

This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (Ministry of Science and ICT) (No. 2019R1A2C1086180).

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Author notes

  1. Sumi Yun and Jiwon Koh authors contributed equally to this work.

Authors and Affiliations

  1. Department of Diagnostic Pathology, Samkwang Medical Laboratories, Seoul, Republic of Korea

    Sumi Yun

  2. Department of Pathology, Seoul National University Hospital, Seoul, Republic of Korea

    Jiwon Koh, Yoonjin Kwak & Woo Ho Kim

  3. Department of Pathology, Seoul National University Bundang Hospital, 173-82 Gumiro, Bundang-gu, Gyeonggi-do, Seongnam-si, 463-707, Republic of Korea

    Soo Kyung Nam & Hye Seung Lee

  4. Department of Pathology, Seoul National University College of Medicine, Seoul, Republic of Korea

    Yoonjin Kwak, Woo Ho Kim & Hye Seung Lee

  5. Department of Surgery, Seoul National University Bundang Hospital, Seongnam, Republic of Korea

    Sang-Hoon Ahn, Joong Do Park & Hyung-Ho Kim

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  1. Sumi Yun
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Contributions

SY and JK performed analysis, interpretation of data, and wrote the manuscripts. SKN, YK, and WHK performed experiments and editing the manuscript. SHA, DJP, and HHK were involved in patient inclusion, material collection, and reviewed the manuscript. HSL design, interpretation of data, critically reviewed the manuscript. All authors read and approved the final manuscript.

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Correspondence to Hye Seung Lee.

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All human tissue samples for research were anonymously coded and experiments were approved by the institutional review board of Seoul National University Bundang Hospital (IRB No. B-1606/349–308).

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Yun, S., Koh, J., Nam, S.K. et al. Immunoscore is a strong predictor of survival in the prognosis of stage II/III gastric cancer patients following 5-FU-based adjuvant chemotherapy. Cancer Immunol Immunother 70, 431–441 (2021). https://doi.org/10.1007/s00262-020-02694-6

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