期刊
CANCER IMMUNOLOGY IMMUNOTHERAPY
卷 69, 期 9, 页码 1751-1766出版社
SPRINGER
DOI: 10.1007/s00262-020-02575-y
关键词
Immunotherapy; Primary central nervous system lymphoma; PCNSL; Tumor microenvironment; TME; TILS
资金
- KU Leuven [3M040406, OT14/101]
- UZ Leuven [RT0817]
- Stichting Me To You
- KU Leuven (Department of Imaging and Pathology)
- Fonds Vandevordt-Gaul
- Stefanie's Rozen fonds
- Fonds Tom Debackere
- 'Emmanuel van der Schueren fellowship' from 'Kom op tegen Kanker'
- Mandate for Fundamental and Translational Research from the 'Stichting tegen Kanker' [2014-083, 2019-091]
- International Roche Chair in hematology
Primary central nervous system lymphoma (PCNSL) is a rare type of non-Hodgkin lymphoma with an aggressive clinical course. To investigate the potential of immune-checkpoint therapy, we retrospectively studied the tumor microenvironment (TME) using high-plex immunohistochemistry in 22 PCNSL and compared to 7 secondary CNS lymphomas (SCNSL) and 7 other CNSL lymphomas with the presence of the Epstein-Barr virus and/or compromised immunity. The TME in PCNSL was predominantly composed of CD8+ cytotoxic T cells and CD163+ phagocytes. Despite molecular differences between PCNSL and SCNSL, the cellular composition and the functional spectrum of cytotoxic T cells were similar. But cytotoxic T cell activation was significantly influenced by pre-biopsy corticosteroids intake, tumor expression of PD-L1 and the presence of EBV. The presence of low numbers of CD8+ T cells and geographic-type necrosis each predicted inferior outcome in PCNSL. Both M1-like (CD68 + CD163(low)) and M2-like (CD68 + CD163(high)) phagocytes were identified, and an increased ratio of M1-like/M2-like phagocytes was associated with a better survival. PD-L1 was expressed in lymphoma cells in 28% of cases, while PD1 was expressed in only 0.4% of all CD8+ T cells. TIM-3, a marker for T cell exhaustion, was significantly more expressed in CD8(pos)PD-1(pos) T cells compared to CD8(pos)PD-1(neg) T cells, and a similar increased expression was observed in M2-like pro-tumoral phagocytes. In conclusion, the clinical impact of TME composition supports the use of immune-checkpoint therapies in PCNSL. Based on observed differences in immune-checkpoint expression, combinations that boost cytotoxic T cell activation (by blocking TIM-3 or TGFBR1) prior to the administration of PD-L1 inhibition could be of interest.
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