FKBP51s: a new molecular biomarker for glioblastoma? Evaluation of pre- and post-operatory blood levels of the FKBP51s protein and correlation with the Magnetic Resonance phenotype.

Congress:

ECR 2020

Poster Number:

C-10493

Type:

Scientific Exhibit

Keywords:

Oncologic Imaging, CNS, MR, Imaging sequences, Neoplasia, Prospective, Diagnostic or prognostic study, Multicentre study

Authors:

C. Giordano¹, S. Cottonaro², P. Guadalupi³, A. Marrazzo³, S. Gaudino⁴, M. F. romano¹, C. Colosimo⁴; ¹Napoli/IT, ²Catania/IT, ³Roma/IT, ⁴Rome/IT

DOI:

10.26044/ecr2020/C-10493

DOI-Link:

https://dx.doi.org/10.26044/ecr2020/C-10493

Fig. 1: Fig.1: Evaluation of the necrotic aspect at MR imaging; sequentially T2, T1 and...

$Fig. 2: Fig 2: CD4 and CD8 T lymphocyte counts and their respective FKBP51s + fractions, in patients (GBM) and control subjects (Control). Although the CD4 FKBP51s subpopulation appears to be increased in patients compared to controls, this increase was not significant References: Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università Federico II, Napoli, Italia$

Fig. 2: Fig 2: CD4 and CD8 T lymphocyte counts and their respective FKBP51s +...

Fig. 3: Table I: Total Treg and Treg FKBP51s + counts in patients with GBM, in relation...

Fig. 4: Fig 3 Study of monocytes in GBM patients. A) Increased counts of CD163+...

Purpose

Recently,ourgrouphasidentifiedaproteinthatisasplicevariantof the FKBP51immunofillin.Immunophillisareproteinsphysiologicallyexpressedby thecellsof the immunesystem. Thesplicevariant,calledFKBP51s,isgeneratedby theactivationofimmunosuppressivecircuitstriggeredby the so-called"immunecheckpointsinhibitors”(inparticularPD-L1/PD1). Anincreasedexpressionof FKBP51sappearsto beassociatedwith aconditionofreducedactivityof the immunesystem. Theaimofourworkwastomeasurethelevelsof the FKBP51sproteininperipheralbloodmononuclearcells(PBMC) ofpatientswith GBM andevaluatepossibleassociationsof theimmunophenotypewith theexpressionof PD-L1 and theMRphenotypeof thetumor.

Methods and materials

Prospectivebicentricstudy. Sevenpatients(5 M and 2F)agedbetween52 and 78wereenrolled,allwith adiagnosisof glioblastoma,whounderwentmacroscopicallycompletesurgicalremoval. FKBP51slevelsweremeasuredinlymphocytes(CD3/CD4, CD3/CD8 and CD4/CD25/Foxp3Treg) and in CD14monocytes(expressingthe M2 marker CD163) 24-48 hoursbeforesurgeryand 1-3monthslater. Thebloodvalueswerecomparedwiththoseof 11subjectsof thesameagewith a negativeoncologicalhistory.Pre-operative MRwasevaluatedtocategorizemorphologicalfeatures(site, edema,hemorrhage,microbleeds,necrosis,calcifications,contrast-enhancement).Post-operative MR was evaluated to assess the presence of residual tumor after surgery. Follow-up MRwere evaluated to controlregression/disappearance, stability, disease progression.

Results

Figure 1shows themorphologicalcharacteristicsof thestudiedcasesin MRI, a scorewasassignedto thenecroticaspect on a scale ranging from a minimum of 1 to a maximum of 3.The evaluation of the necroticaspect at MR imaging was based on T2, T1 and T1 after contrast weighted images. Nodifferenceswerefoundbetweenpatientsandcontrolsin the CD4 and CD8 T-cellcounts,bothtotaland FKBP51s-expressingsubsets.Althoughthe CD4 FKBP51ssubpopulationappearsto beincreasedin patientscomparedtocontrols,thisincreasewasnotsignifican. TotalTregandTregFKBP51scountsshow asignificantincreaseinpatientscomparedto controlsubjects. Ofparticularinterestistheincreasein theTregFKBP51scountinpatientswhoshow positiveimmunohistochemistryfor the PD-L1 marker,comparedwithpatientsinwhomthe PD-L1signalisabsent(TableI). Wefoundasignificantincreaseinmonocytesexpressingthe CD163 marker inpatientscomparedtocontrols(Figure 3A).Thismarkerisassociatedwith an alternativepolarizationprofileor M2whichcharacterizesmonocyteswithimmunosuppressiveactivity. CD163 +monocytes, in GBMpatients,expressedFKBP51s tovaryingdegrees.Figure 3Bshows thecytofluorimetricphenotypesof themonocytesof thecasesrepresentedin Figure 1. In the G2phenotype, the ratiobetweenthe...

Conclusion

Althoughstillverypreliminary,ourdatasuggestthattheexpressionof PD-L1 on GBMisaccompaniedby anexpansionof aregulatoryT subsetexpressingFKBP51s.Theseresultsappearto be in line with datapreviouslyobtainedinpatientswith melanoma. Thestudyalsosuggestsastrictrelationshipbetweena CD14/CD163/FKBP51smonocyte-macrophagesubpopulationand the MRphenotypeoftumornecrosis. The release oftumorantigens,producedbynecrosis,couldbe theprimarycause of thedevelopmentofthesepeculiarleukocytes,asaresultof atumor/immunesysteminteractionwithpossiblediagnosticandprognosticvalue.Thereis also asignificantincrease ofthe CD163/FKBP51ssubpopulation,after surgical removal, in patients in which was found the presenceofresidualtumor, so in the future can beuseful take in account this molecolar biomarker also in post-surgery evaluation and in the follow-up.

Personal information and conflict of interest

C. Giordano; Naples/IT - nothing to disclose S. Cottonaro; Catania/IT - nothing to disclose P. Guadalupi; Rome/IT - nothing to disclose A. Marrazzo; Rome/IT - nothing to disclose S. Gaudino; Rome/IT - nothing to disclose M. F. Romano; Naples/IT - nothing to disclose C. Colosimo; Rome/IT - nothing to disclose

References

www.impactjournals.com/oncotarget/Oncotarget, 2017, Vol. 8, (No. 40), pp: 68291-68304A regulatory role for the co-chaperone FKBP51s in PD-L1 expression in glioma Paolo D’Arrigo1,*, Michele Russo1,*, Anna Rea1, Martina Tufano1, Elia Guadagno2, Maria Laura Del Basso De Caro2, Roberto Pacelli2, Felix Hausch3, Stefania Staibano2, Gennaro Ilardi2, Silvia Parisi1, Maria Fiammetta Romano1 and Simona Romano1 Cancer Immunol Immunother DOI 10.1007/s00262-017-2004-0FKBP51s signature in peripheral blood mononuclear cells of melanoma patients as a possible predictive factor for immunotherapySimona Romano1· Ester Simeone2· Anna D’Angelillo1· Paolo D’Arrigo1· Michele Russo1· Mario Capasso1,3· Vito Alessandro...