Clinicopathological analysis of immunohistochemical expression of immune checkpoint molecules in follicular lymphoma.

Abstract

Follicular lymphoma (FL) is characterized by an indolent clinical course and a high relapse rate, and often exhibits a diffuse pattern beyond the follicular area. Our group previously reported that immune checkpoint (ICP) pathways, such as programmed cell death (PD-1) and programmed death ligand 1 (PD-L1), are poor prognostic factors for diffuse large B-cell lymphoma and adult T-cell leukemia/lymphoma. In this study, the association between the expression of multiple ICP molecules according to immunohistochemistry and clinicopathological features in FL was determined via immunostaining of 173 biopsy samples. Membrane and/or cytoplasm expression of CD86 (nCD86) and PD-L1 (nPD-L1) was found in tumor cells, whereas PD-1 (miPD-1), Galectin-9 (miGalectin-9), OX40 (miOX40), CTLA-4 (miCTLA-4), Tim-3 (miTim-3), OX40L (miOX40L), and LAG-3 (miLAG-3) were expressed in non-neoplastic stromal cells. MiPD-1 expression was significantly higher in the follicular area than in the diffuse area (p = 0.0450). Expression of miOX40 and miCTLA-4 was significantly higher in the diffuse area than in the follicular area (respectively, p = 0.0053 and p = 0.0092). MiTim-3 tended to be higher in the diffuse area than in the follicular area (p = 0.0616). MiTim-3 was significantly higher in relapse cases than in new-onset cases (p = 0.0440); miLAG-3 tended to be higher in relapse cases than in new-onset cases (p = 0.0622, not significant). The miOX40L-high FL group had a significantly worse overall survival than the miOX40L-low group (p = 0.0320). The expression of multiple ICP molecules on several cells reflects activated anti-tumor immunity and the unique FL microenvironment. Further studies on gene expression or genomic abnormalities will reveal the clinical and biological significance of ICP molecules in FL.

• Authors: Eriko Yanagida, Hiroaki Miyoshi, Mai Takeuchi, Joji Shimono, Kazutaka Nakashima, Kyohei Yamada, Keisuke Kawamoto, Mayuko Moritsubo, Yasumasa Shimasaki, Kanako Inoue, Teppei Imamoto, Takuya Furuta, Kei Kohno, Koichi Ohshima
• Journal: Hematological oncology (Hematol Oncol) Vol. 40 Issue 4 Pg. 530-540 (Oct 2022) ISSN: 1099-1069 [Electronic] England
• PMID: 35122292 (Publication Type: Journal Article)
• Copyright: © 2022 John Wiley & Sons Ltd.

Chemical References

• B7-H1 Antigen
• Biomarkers, Tumor
• CTLA-4 Antigen
• Galectins
• Hepatitis A Virus Cellular Receptor 2
• Immune Checkpoint Proteins
• Programmed Cell Death 1 Receptor

Topics

• Adult
• B7-H1 Antigen (metabolism)
• Biomarkers, Tumor (metabolism)
• CTLA-4 Antigen
• Galectins
• Hepatitis A Virus Cellular Receptor 2
• Humans
• Immune Checkpoint Proteins
• Lymphoma, Follicular
• Lymphoma, Large B-Cell, Diffuse (pathology)
• Prognosis
• Programmed Cell Death 1 Receptor (metabolism)
• Recurrence
• Tumor Microenvironment