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In-depth characterization of the tumor microenvironment in central nervous system lymphoma reveals implications for immune-checkpoint therapy
- Source :
- Cancer Immunology, Immunotherapy. 69:1751-1766
- Publication Year :
- 2020
- Publisher :
- Springer Science and Business Media LLC, 2020.
-
Abstract
- 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 + CD163low) and M2-like (CD68 + CD163high) 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 CD8posPD-1pos T cells compared to CD8posPD-1neg 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.
- Subjects :
- Male
Herpesvirus 4, Human
Cancer Research
Lymphoma
medicine.medical_treatment
CD8-Positive T-Lymphocytes
Central Nervous System Neoplasms
0302 clinical medicine
hemic and lymphatic diseases
Tumor Microenvironment
Immunology and Allergy
Cytotoxic T cell
Primary central nervous system lymphoma
Child
Aged, 80 and over
Middle Aged
medicine.anatomical_structure
Oncology
Female
Immunotherapy
TILS
Adult
Adolescent
T cell
Immunology
Antigens, Differentiation, Myelomonocytic
Receptors, Cell Surface
Young Adult
03 medical and health sciences
Lymphocytes, Tumor-Infiltrating
Antigens, CD
Biomarkers, Tumor
medicine
Humans
PCNSL
Aged
Retrospective Studies
Tumor microenvironment
business.industry
TME
medicine.disease
Immune checkpoint
Cancer research
business
CD8
T-Lymphocytes, Cytotoxic
030215 immunology
Subjects
Details
- ISSN :
- 14320851 and 03407004
- Volume :
- 69
- Database :
- OpenAIRE
- Journal :
- Cancer Immunology, Immunotherapy
- Accession number :
- edsair.doi.dedup.....94a5027aa06ee1537889ec6da46be04e