New paths for cancer therapy

With his Inter­natio­nal Junior Rese­arch Group "Lo­cal im­mune con­trol of cancer within the tumor microen­vironment", Dr. Jan Bött­cher and his team at the Klini­kum recht der Isar of the Tech­nical Uni­versi­ty on Mu­nich are rese­ar­ching new stra­tegies for the suc­cess­ful im­muno­thera­py of cancer pati­ents. Re­cently, the group achie­ved a re­markable rese­arch suc­cess.

Den­dritic cells are an essen­tial part of our im­mune sys­tem and are able to or­gan­ise im­mune re­sponses against viral infec­tions and can­cers. In tu­mours, how­ever, these cells are often dys­func­tion­al, limit­ing their abil­ity to or­gan­ise effec­tive anti-cancer im­muni­ty and tumor con­trol. The Inter­na­tional Junior Re­search Group of Dr. Jan Böt­tcher has now un­cov­ered a pre­vious­ly un­known mechanism by which den­dritic cells are switched off in tu­mour tis­sue. This is medi­ated by the bioac­tive lipid pros­ta­glandin E2 (PGE2) pro­duced by tu­mour cells, whereby den­dritic cells are re­pro­grammed local­ly in the tu­mour and can no long­er com­muni­cate with so-called tu­mour-infil­trat­ing cyto­toxic T cells. Fur­ther­more, Dr Böt­tcher's re­search group was able to demonstrate that this inhib­itory mechanism can be re­versed by blocking PGE2 recep­tors on the sur­face of den­dritic cells, there­by ena­bling an im­proved im­mune re­sponse against the tu­mour. These find­ings point to new ave­nues for the de­velopment of better im­mu­no­thera­pies to fight can­cer.

The origi­nal publi­cation can be viewed online: Bayerl F., Meiser P., Do­na­konda S., Hirschberger A., Lach­er S., Pedde A.M., Her­mann C.D., Knolle M., Ru­dolph T.J., Grassmann S., Öllinger R., Kirchham­mer N., Trefny M., Elewaut A., Anton M., Wohlleber D., Höchst B., Za­remba A., Krüger A., Rad R., Obenauf A.C., Schaden­dorf D., Zip­pelius A., Buchholz V.R., Schraml B.U. and Böt­tcher J.P. (2023).Tumor-derived PGE2 pro­grams cDC1 dys­func­tion to im­pair intra­tu­moral or­ches­tra­tion of anti-cancer T cell re­sponses. Im­muni­ty. DOI: 10.1016/j.immuni.2023.05.011

Text: Dr. Jan Böttcher