Pathological Findings of the Host Immune Reaction in the Tumor Microenvironment of Gastroenteropancreatic Neuroendocrine Neoplasms
| Autor: | Kunihiro Hosono, Atsushi Nakajima, Itaru Endo, Yusuke Kurita, Takamitsu Sato, Ayumu Goto, Noritoshi Kobayashi, Sho Hasegawa, Motohiko Tokuhisa, Yasushi Ichikawa, Naoki Okubo |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Lymphocyte
030204 cardiovascular system & hematology immune checkpoint system T-cell markers B7-H1 Antigen 03 medical and health sciences 0302 clinical medicine Immune system Lymphocytes Tumor-Infiltrating Stomach Neoplasms Internal Medicine PMS2 Biomarkers Tumor Tumor Microenvironment Medicine Humans Tumor microenvironment business.industry FOXP3 General Medicine Immune checkpoint MSH6 Neuroendocrine Tumors medicine.anatomical_structure MSH2 Cancer research 030211 gastroenterology & hepatology Original Article business GEP-NEN (gastroenteropancreatic neuroendocrine neoplasms) |
| Zdroj: | Internal Medicine |
| ISSN: | 1349-7235 0918-2918 |
| Popis: | Objective Neuroendocrine neoplasms (NENs) are rare and indolent diseases, but the efficacy of treatment without surgical resection is temporary and limited. Targeted immunotherapy is an important treatment strategy in several cancers. However, the tumor and host immune reactions in the NEN microenvironment are poorly understood. Therefore, we investigated the immune checkpoint system and host immune response in pathological NEN specimens. Methods The expression of the mismatch repair proteins MSH2, MSH6, PMS2, and MLH1 was immunohistochemically detected in archival tissue samples obtained from 20 patients with gastroenteropancreatic NENs. We additionally assessed the expression of programmed death (PD)-1, PD-L1, and the tumor-infiltrating lymphocyte (TIL) markers CD8 and family of transcription factor P3 (FOXP3). Results All 20 NENs expressed the mismatch repair proteins MSH2, MSH6, PMS2, and MLH1. The PD-L1 and/or PD-1 expression in the tumor cells and/or TILs was confirmed in 75% of the cases. PD-1-, CD8-, and FOXP3-positive TILs were more frequently associated with PD-L1-positive tumors than with PD-L1 negative tumors (PD-1: 19.5 vs. 7.3, CD8: 18.1 vs. 7.1, FOXP3: 13.2 vs. 3.2, p=0.438, p=0.419, P=0.603, respectively). The number of cells positive for PD-1 tended to gradually increase in increasing grade of NENs but did not reach significance (Grade 1: 5.8, Grade 2: 10.2, NEC: 18.1, p=0.903). Conclusion NENs consistently express mismatch repair proteins but have a high expression of PD-L1 and/or PD-1 in the tumor microenvironment. NEC and PD-L1-positive NENs may be immunologically "hot" tumors, so an immunological approach may be an appropriate treatment strategy for these tumors. |
| Databáze: | OpenAIRE |
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