Abstract 525P
Background
Glioblastoma (GBM) is characterized by an “immune-deserted” tumor microenvironment (TME) consisting of tumor-associated macrophages (TAMs) and tumor infiltrating lymphocytes (TILs). We aimed to investigate the prognostic role of tumor tissue markers correlating with overall survival (OS) and progression-free survival (PFS).
Methods
By immunohistochemistry (IHC), we analyzed on 31 archival formalin-fixed paraffin embedded (FFPE) tissue specimens: CD3, CD4, CD8, CD20, CD45, CD68, CD163, CD66b and PDL-1. Expression values were classified according to density score from 0 to 4 (0=no expression; 1=1-25%; 2=26-50%, 3=51-74%; 4=75%-100%) in two areas: Vascular/perivascular (V) and diffuse in tumor parenchyma (D). Percentage of infiltrating immune system cell was calculated by the rate of absolute number of positive stained cells/total number of cells multiplied by 100.
Results
All tissues were negative for PDL1 and only two positive for CD20. We observed that CD68+ macrophage and CD66b+ neutrophils expressed in V showed a statistically significant prognostic role (p-value of 0.027 and 0.029 respectively) (Table). CD68-V showed a prognostic role for PFS (p-value 0.032), while CD66b-V expression did not. CD3, CD4, CD8, CD45 and CD163 were not associated with OS and PFS.
Table: 525P
| Characteristics | Univariable models OS | Multivarible model OS | Univariable models PFS | Multivarible model PFS | ||||
| HR (95%CI) | P-value | HR (95%CI) | P-value | HR (95%CI) | P-value | HR (95%CI) | P-value | |
| CD68V | ||||||||
| 0-1 | 1.00 | - | 1.00 | - | 1.00 | - | 1.00 | - |
| 2-4 | 0.42 (0.19-0.91) | 0.027 | 0.46 (0.21-0.99) | 0.049 | 0.41 (0.18-0.92) | 0.032 | 0.45 (0.20-1.01) | 0.054 |
| CD66bV | ||||||||
| 0-1 | 1.00 | - | 1.00 | - | 1.00 | - | 1.00 | - |
| 2-4 | 0.38 (0.16-0.90) | 0.029 | 0.41 (0.17-0.98) | 0.046 | 0.45 (0.17-1.12) | 0.087 | 0.49 (0.19-1.24) | 0.136 |
Conclusions
Despite having a smaller cohort of tissues, we showed a different expression of immune markers. In particular, CD68-V was associated with a significant positive impact on both OS and PFS. This relation could be partially explained because TAM do not raise only from peripheral blood, but also from resident microglia. Moreover, we observed high density of CD66b+ cells in V related to OS probably for growth factors overproducted by tumor cells with their recruitment from blood. Further studies are needed in large series to explore the prognostic role of selected TME immune molecules to develop therapeutic strategies that aim to hit different components of GBM.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
IRST and Area Vasta Romagna Ethics Committee.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
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