P-0035 - Immunosuppressive protein expression on tumor and the presence of immune cells within tumor microenvironment in curatively resected gastric cancer

Date 28 June 2014
Event World GI 2014
Session Poster Session
Topics Gastric Cancer
Cancer Immunology and Immunotherapy
Pathology/Molecular Biology
Presenter Won Kim Jin
Citation Annals of Oncology (2014) 25 (suppl_2): ii14-ii104. 10.1093/annonc/mdu165
Authors W. Kim Jin1, J. Lee2, J. Kim Yu3, K. Lee2, H. Kim Jee2, S. Bang2, S. Lee Jong2, H. Nam Kyung4, S. Lee Hye4, S. Ahn5, J. Park Do5, H. Kim6, S. Kim2
  • 1Division of Hematology and Medical Oncology, Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam-si/KI
  • 2Division of Hematology and Medical Oncology, Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam-si/KR
  • 3Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam-si/KR
  • 4Department of Pathology, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam-si/KR
  • 5Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam-si/KR
  • 6Seoul National University Bundang Hospital, Seongnam-si/KR

Abstract

Introduction

Evading immune destruction is a hallmark of biological capabilities in cancer development. Superficially, the presence of immune cells in tumor microenvironment might be response of host to combat tumors. Immunosuppressive protein on tumor might act to evade host immune surveillance. We evaluated the association among immunosuppressive proteins on tumor and the presence of immune cells in tumor microenvironment and identified their clinical implication.

Methods

Of 289 patients with gastric cancer who received curative resection, 243 patients were available for tissue specimens. Expression of programmed cell death 1 ligand 1 (PD-L1), cytotoxic T-lymphocyte antigen 4 (CTLA-4) and indoleamine 2,3-dioxygenase (IDO) on tumor was identified as negative, weak, moderate, or strong staining intensity using immunohistochemistry of tissue microarray. Specimens were recorded as positive when >10% of tumor cells showed moderate to strong staining intensity for PD-L1, CTLA-4 and IDO. The densities of CD3+ and PD-1+ cells within tumor stroma including tumor were assessed using an image analysis system to evaluate the presence of immune cells in tumor microenvironment. Specimens over median density were defined as ‘rich’ group of immune cell in tumor microenvironment. Clinical data and pathologic results were retrieved from electronic medical record.

Results

Of 243 patients with gastric cancer, 106 (43.6%), 160 (65.8%) and 116 patients (47.7%) showed positive expression of PD-L1, CTLA-4 and IDO, respectively. The positive expression of PD-L1, CTLA-4 and IDO were frequently showed in less advanced stage (p = 0.047, p = 0.016, p = 0.007, respectively), intestinal type (p = 0.003, p = 0.003, p < 0.001, respectively) and moderate differentiation (p = 0.007, p = 0.011, p = 0.001, respectively). Tumors with CD3+ and PD1+ ‘rich’ microenvironment had the association with diffuse type (p = 0.021, p = 0.058, respectively) and poorly differentiated or signet ring cell type (p = 0.062, p = 0.022, respectively). There was strong correlation among positive expressions of PD-L1, CTLA-4 and IDO on tumor. However, no relationship between expressions of PD-L1, CTLA-4 and IDO on tumor and CD3+ and PD-1+ cell ‘rich’ microenvironment was shown. PD-L1 positive tumor and CD3+ cell ‘rich’ microenvironment had longer disease-free survival and overall survival (p = 0.016, p = 0.006, respectively). In multivariate analysis, these remained better prognostic values (disease-free survival: risk ratio =0.582 (0.372-0.910), p = 0.018, risk ratio = 0.624 (0.399-0.976), p = 0.038, respectively; overall survival: risk ratio= 0.651 (0.416-1.017), p = 0.059, risk ratio= 0.538 (0.347-0.832), p = 0.005, respectively).

Conclusion

In gastric cancer, immunosuppressive protein of PD-L1, CTLA-4 or IDO is frequently expressed. Tumors with positive expression of PD-L1, CTLA-4 and IDO and with CD3+ and PD1+ ‘rich’ microenvironment have a distinct clinicopathologic group. There is no relationship between expression of PD-L1, CTLA-4 and IDO on tumor and CD3+ and PD-1+ cell ‘rich’ microenvironment. PD-L1 expression on tumor and CD3+ cell ‘rich’ microenvironment are better prognostic markers independently.