Cancer study provides approaches for new immunotherapies

As part of a project fund­ed by the Wil­helm Sander Foun­da­tion, researchers at the Med­ical Fac­ul­ty of the Uni­ver­si­ty of Duis­burg-Essen have stud­ied glioblas­tomas, the most aggres­sive brain tumors in adults, and dis­cov­ered stem cells of the hematopoi­et­ic sys­tem there for the first time. The team from the DKTK part­ner site in Essen/Düsseldorf found that these blood stem cells pro­mote the divi­sion of can­cer cells and sup­press the immune defense against the tumor. Their dis­cov­ery could help devel­op more effec­tive immunother­a­pies against brain tumors. The study was pub­lished in Nature Com­mu­ni­ca­tions and includ­ed in Edi­tors’ High­lights and the Can­cer at Nature Portfolio.

Glioblas­tomas are brain tumors with a par­tic­u­lar­ly severe and usu­al­ly fatal course. They are usu­al­ly not suc­cess­ful­ly treat­able in the long term, even with the best pos­si­ble sur­gi­cal, chemother­a­peu­tic and radio­ther­a­peu­tic treat­ments. Even immunother­a­pies, which already achieve good results with oth­er types of can­cer, do not work. The caus­es are still not clear­ly under­stood, mak­ing research into the under­ly­ing mech­a­nisms all the more important.

In a research project fund­ed by the Wil­helm Sander Foun­da­tion, the team led by can­cer researcher Dr. Igor Cima and Prof. Dr. Björn Schef­fler, DKTK Pro­fes­sor of Trans­la­tion­al Oncol­o­gy at the West Ger­man Tumor Cen­ter (WTZ) of the Uni­ver­si­ty Hos­pi­tal Essen (UK Essen), exam­ined sam­ples of glioblas­tomas and of healthy brain tis­sue. To their sur­prise, the sci­en­tists* dis­cov­ered blood stem cells and pre­cur­sor cells of the hematopoi­et­ic sys­tem, which are nor­mal­ly locat­ed in the bone mar­row, for the first time in all sam­ples of malig­nant brain tis­sue. This cell type was not detectable in healthy tis­sue samples.

“Glioblas­tomas pro­duce immuno­sup­pres­sive mes­sen­gers, and in the imme­di­ate microen­vi­ron­ment of the tumors are found cer­tain types of immune cells that specif­i­cal­ly throt­tle the body’s own defens­es. In our cell cul­ture assay sys­tems, hematopoi­et­ic stem cells were able to fur­ther increase the divi­sion activ­i­ty of the can­cer cells, while at the same time the tumor cells increased the pro­duc­tion of the mol­e­cule PD-L1 (pro­grammed cell death 1 lig­and 1), known as an “immune brake”, on their surface.”

- Björn Scheffler

 

The researchers exam­ined a total of sev­er­al hun­dred tis­sue sam­ples from glioblas­toma patients. The result: the more blood stem cells a tumor con­tained, the more immuno­sup­pres­sive mes­sen­ger sub­stances were released, the more immune-brak­ing mark­ers the can­cer cells formed — and the low­er the over­all sur­vival of those affected.

In addi­tion, the team, in coop­er­a­tion with Prof. Dr. Ulrich Sure, Direc­tor of the Clin­ic for Neu­ro­surgery at the UK Essen, com­pared healthy with dis­eased cells. By sequenc­ing the gene expres­sion of 660 indi­vid­ual cells from vital tumor tis­sue, pro­files could be gen­er­at­ed and com­pared to cells from healthy bone mar­row and blood. Analy­sis of these data reveals some new approach­es to ren­der­ing the tumor-pro­mot­ing cell pop­u­la­tion under study harm­less in the future.

The fact that blood stem cells in the bone mar­row pref­er­en­tial­ly mature into immuno­sup­pres­sive cell types dur­ing the course of can­cer, by being pro­grammed accord­ing­ly by the tumor, was already known to researchers. Can­cer researcher Igor Cima now sus­pects a sim­i­lar phe­nom­e­non in glioblas­toma-asso­ci­at­ed hematopoi­et­ic stem cells: “For the first time, we now see the pos­si­bil­i­ty of mod­u­lat­ing the dif­fer­en­ti­a­tion process of glioma-asso­ci­at­ed hematopoi­et­ic stem cells in the course of fur­ther research projects — for exam­ple, by using cer­tain cell mes­sen­gers — and thus cir­cum­vent­ing the tumor-induced immune block­ade. Then immunother­a­pies would also have a bet­ter chance of being effec­tive against glioblastoma.”

The research team’s find­ings were recent­ly pub­lished in the pres­ti­gious jour­nal Nature Com­mu­ni­ca­tions and were also includ­ed in the Edi­tors’ High­t­lights in Focus Can­cer and also in the cross-jour­nal Can­cer at Nature portfolio.

Wilhelm Sander Foundation: Partner of innovative cancer research

The Wil­helm Sander Foun­da­tion sup­port­ed the research project with approx­i­mate­ly 191,000 euros.
The pur­pose of the foun­da­tion is to pro­mote med­ical research, in par­tic­u­lar projects in the field of can­cer. Since the foun­da­tion was estab­lished, a total of more than 250 mil­lion euros has been dis­bursed for research fund­ing in Ger­many and Switzer­land. This makes the Wil­helm Sander Foun­da­tion one of the most impor­tant pri­vate research foun­da­tions in Ger­many. It emerged from the estate of the entre­pre­neur of the same name, who died in 1973.

About the West German Tumor Center

At the West Ger­man Tumor Cen­ter (WTZ), patients can ben­e­fit not only from the best pos­si­ble diag­nos­tics and ther­a­py, but also from the fact that promis­ing approach­es from lab­o­ra­to­ry research are applied in inno­v­a­tive clin­i­cal stud­ies. The WTZ Cen­ter for Neu­roon­col­o­gy unites more than 10 clin­ics and insti­tutes of the Uni­ver­si­ty Med­ical Cen­ter Essen in an inter­dis­ci­pli­nary way. Con­tact per­sons are Prof. Dr. Ulrich Sure (Direc­tor of the Depart­ment of Neu­ro­surgery and Spine Surgery), Prof. Dr. Mar­tin Glas (Head of the Divi­sion of Clin­i­cal Neu­roon­col­o­gy at the Depart­ment of Neu­rol­o­gy) and Prof. Dr. Björn Schef­fler (Direc­tor of the DKFZ Depart­ment of Trans­la­tion­al Neu­roon­col­o­gy at the WTZ).

About the German Consortium for Translational Cancer Research (DKTK)

In the DKTK, the Ger­man Can­cer Research Cen­ter (DKFZ) in Hei­del­berg, as the core cen­ter, joins forces on a long-term basis with uni­ver­si­ty part­ner sites in Ger­many that have a par­tic­u­lar­ly high rep­u­ta­tion in oncol­o­gy. With more than 3,000 employ­ees, the DKFZ is the largest bio­med­ical research insti­tu­tion in Ger­many. The sci­en­tists inves­ti­gate how can­cer devel­ops, iden­ti­fy risk fac­tors and search for new strate­gies to pre­vent peo­ple from devel­op­ing can­cer. They devel­op new meth­ods with which tumors can be diag­nosed more pre­cise­ly and those affect­ed can be treat­ed more successfully.