Table 1.

Overview of published studies investigating the TME in PCNSL [3, 8–15, 22]

Study (references)	Year	DLBCL-PCNSL patients	Conclusions
Ponzoni et al. [7]	2007	96	Presence of reactive perivascular CD3+ T cell infiltrate is associated with ↑ OS. Presence of tumor necrosis has no prognostic significance
Kumari et al. [8]	2009	30	Reactive perivascular CD3+ T cell infiltrate shows no correlation with the different IELSG risk score groups. Tumor necrosis shows no correlation with the different IELSG risk score groups
Komohara et al. [9]	2011	43	The number of infiltrating CD68+, CD163+ and CD204+ TAMs has no prognostic significance.
He et al. [10]	2013	62	Presence of reactive perivascular CD3+ T cell infiltrate is associated with ↑ OS. Presence of aggregative perivascular tumor cells, stained with XBP1 and CD44, is associated with ↓ OS
Chang et al. [3]	2015	32 (+ 30 non-CNS DLBCL)	PCNSL has a ↓ OS in comparison with non-CNS DLBCL. PCNSL shows ↓ HLA-DR expression, ↓ number of S100+ dendritic cells, ↓ number of CD45RO+ effector or memory T cells in comparison with non-CNS DLBCL. For PCNSL patients, ↓ number of infiltrating granzyme B+ CTL correlated with ↓ OS
Four et al. [11]	2016	32	Expression of PD-1 in CTLs and PD-L1 in tumor cells was observed in higher rates compared with non-CNS DLBCL. PD-1 expression in CTLs correlated with PD-L1 expression in tumor cells. Presence of PD-1+ CTLs is associated with ↓ OS
Sasayama et al. [12]	2016	47	The number of infiltrating CD204+ TAMs shows no prognostic significance. ↑ number of CD68+ TAMs correlates with ↓ PFS on univariate analysis. Trends were observed for ↑ number of CD163+ TAMs and ↓ PFS on univariate analysis. The number of infiltrating CD68+ and CD163+ TAMs shows no prognostic significance on multivariate analysis
Cho et al. [13]	2017	76	↑ expression of CD68+ TAMs is associated with ↓ OS and ↓ PFS. FoxP3 expression in Tregs has no prognostic significance
Cho et al. [14]	2017	76	PD- 1 expression is associated with inferior OS
Miyasato et al. [20]	2018	5	PD-L1 and IDO1 were overexpressed by macrophage/microglia in PCNSL

TME tumor microenvironment, PCNSL primary central nervous system (CNS) lymphoma, OS overall survival, IELSG International Extranodal Lymphoma Study Group, TAM tumor-associated macrophage, DLBCL diffuse large B-cell lymphoma, CTL cytotoxic T cell, PFS progression-free survival, Treg regulatory T cell