Immune Monitoring Unit

Specific immunotherapy is a promising treatment option for various tumor patients. Immunotherapeutic strategies comprise the vaccination of tumor peptides and immunostimulatory adjuvants, the application of monoclonal and bispecific antibodies as well as the adoptive transfer of non-modified and chimeric antigen receptor- or T cell receptor-engineered T lymphocytes. 

The concomitant monitoring of the frequency, phenotype and functional properties of different immune cell populations is of essential importance to understand clinical responses and side effects caused by the treatment. Moreover, immune monitoring enables the identification of novel treatment-related prognostic and predictive biomarkers.

The major task of the immune monitoring unit is the analysis of the phenotype and functional properties of different immune cell populations in the context of clinical trials. Moreover, such studies support the design of improved immunotherapeutic strategies for tumor patients.

Service (selection)

  • Monitoring of different immune cell populations in the patient blood during clinical studies
  • Phenotypic and functional characterization of different immune cell populations in tumor samples and tumor-free tissues
  • Consulting service for the design of immune monitoring for translational research projects and clinical studies

Methods

  • Evaluation of tumor peptide-specific T cells (ELISPOT/FACS)
  • Phenotyping of immune cells (FACS/ELISA/Immunohistochemistry/Immunofluorescence)
  • Analysis of autoantibodies (Immunohistochemistry/Immunofluorescence)
  • Functional assays for immune cells [FACS/ELISA/Radioactivity assays (Cr51/3H-Thymidine)]
  • FACS-based single cell sorting
  • T cell cloning
  • T cell receptor sequencing
  • NanoString-®Technology 
  • Transcriptomics
  • HLA typing
  • Magnetic cell separation (MACS)
  • Multispectral imaging platforms (Vectra®, MACSimaTM)
Immune Monitoring

Characterisation of the tumor immune architecture by using the Vectra®3.0 system from PerkinElmer (automated multispectral imaging technology) Copyright: Uniklinik Dresden/Gabriele Bellmann

1.    Tirado-Gonzalez I, Descot A, Soetopo D, Nevmerzhitskaya A, Schäffer A, Kur IM, Czlonka E, Wachtel C, Tsoukala I, Müller L, Schäfer AL, Weitmann M, Dinse P, Alberto E, Buck MC, Landry JJM, Baying B, Slotta-Huspenina J, Roesler J, Harter PN, Kubasch AS, Meinel J, Elwakeel E, Strack E, Tran Quang C, Abdel-Wahab O, Schmitz M, Weigert A, Schmid T, Platzbecker U, Benes V, Ghysdael J, Bonig H, Götze KS, Rothlin CV, Ghosh S, Medhouf H. AXL inhibition in macrophages stimulates host-versus-leukemia immunity and eradicates naïve and treatment resistant leukemia. Cancer Discov. In press

2.    Kießler M, Plesca I, Sommer U, Wehner R, Wilczkowski F, Müller L, Tunger A, Lai X, Rentsch A, Peuker K, Zeissig S, Seifert AM, Seifert L, Weitz J, Bachmann M, Bornhäuser M, Aust D, Baretton G, Schmitz M. Tumor-infiltrating plasmacytoid dendritic cells are associated with survival in human colon cancer. J Immunother Cancer. 2021;9:e001813.

3.    Seifert L, Plesca I, Müller L, Sommer U, Heiduk M, von Renesse J, Digomann D, Glück J, Klimova A, Weitz J, Schmitz M, Seifert AM. LAG-3- expressing tumor-infiltrating T cells are associated with reduced disease-free survival in pancreatic cancer. Cancers. 2021;13:1297   

4.    Berndt N, Bippes CC, Michalk I, Bachmann D, Bachmann J, Puentes-Cala E, Bartsch T, Loureiro LR, Kegler A, Bergmann R, Gross JK, Gross T, Kurien BT, Scofield RH, Farris AD, James JA, Schmitz M, Fahmy K, Feldmann A, Arndt C, Bachmann MP. Two be or not two be: The nuclear autoantigen La/SS-B is able to form dimmers and oligomers in a redox-dependent manner. Int J Mol Sci. 2021;22:3377.

5.    Bachmann MP, Bartsch T, Bippes CC, Bachmann D, Puentes-Cala E, Bachmann J, Bartsch H, Arndt C, Koristka S, Loureiro LR, Kegler A, Laube M, Gross JK, Gross T, Kurien BT, Scofield RH, Farris AD, James JA, Schmitz M, Feldmann A. T cell mediated conversion of a non-anti-La reactive B cell to an autoreactive anti-La B cell by somatic hypermutation. Int J Mol Sci. 2021;22:1198. 

6.    Müller L, Tunger A, Wobus M, von Bonin M, Towers R, Bornhäuser M, Dazzi F, Wehner R, Schmitz M. Immunomodulatory properties of mesenchymal stromal cells: An update. Front Cell Dev Biol. 2021;9:637725.

7.    Seifert AM, Eymer A, Heiduk M, Wehner R, Tunger A, von Renesse J, Decker R, Aust DE, Welsch T, Reissfelder C, Weitz J, Schmitz M, Seifert L. PD-1 expression by lymph node and intratumoral regulatory T cells is associated with lymph node metastasis in pancreatic cancer. Cancers. 2020;12:E2756.

8.    Pearson¬ FE, Tullett KM, Leal-Rojas IM, Haigh OL, Masterman KA, Walpole C, Bridgeman JS, McLaren JE, Ladell K, Miners K, Llewellyn-Lacey S, Price DA, Tunger A, Schmitz M, Miles JJ, Lahoud MH, Radford KJ. Human CLEC9A antibodies deliver Wilms’ tumor 1 (WT1) antigen to CD141+ dendritic cells to activate naïve and memory WT1-specific CD8+ T cells. Clin Transl Immunology. 2020;9:e1141.   

9.    Vadakekolathu J, Minden MD, Hood T, Church SE, Reeder S, Altmann H, Sullivan AH, Viboch EJ, Patel T, Ibrahimova N, Warren SE, Arruda A, Liang Y, Smith TH, Foulds GA, Bailey MD, Gowen-MacDonald J, Muth J, Schmitz M, Cesano A, Pockley AG, Valk PJM, Löwenberg B, Bornhäuser M, Tasian SK, Rettig MP, Davidson-Moncada JK, DiPersio JF, Rutella S. Immune landscapes predict chemotherapy resistance and immunotherapy response in acute myeloid leukemia. Sci Transl Med. 2020;12:eaaz0463.  

10.    Plesca I, Tunger A, Müller L, Wehner R, Lai X, Grimm MO, Rutella S, Bachmann M, Schmitz M. Characteristics of tumor-infiltrating lymphocytes prior to and
during immune checkpoint inhibitor therapy. Front Immunol. 2020;11:364.

11.    Müller L, Tunger A, Plesca I, Wehner R, Temme A, Westphal D, Meier F, Bachmann M, Schmitz M. Bidirectional crosstalk between cancer stem cells and immune cell subsets. Front Immunol. 2020;11:140.

12.    Mitwasi N, Feldmann A, Arndt C, Koristka S, Berndt N, Jureczek J, Loureiro LR, Bergmann R, Mathe D, Hegedüs N, Kovacs T, Zhang C, Oberoi P, Jäger E, Seliger B, Rössig C, Temme A, Eitler J, Tonn T, Schmitz M, Hassel JC, Jäger D, Wels WS, Bachmann M. “UniCAR”-modified off-the-shelf NK-92 cells for targeting to GD2-expressing tumour cells. Sci Rep. 2020;10:2141.

13.    Krüger T, Middeke JM, Stölzel F, Mütherig A, List C, Brandt K, Heidrich K, Teipel R, Ordemann R, Schuler U, Oelschlägel U, Wermke W, Kräter M, Herbig M, Wehner R, Schmitz M, Bornhäuser M, von Bonin M. Reliable isolation of human mesenchymal stromal cells from bone marrow biopsies in patients after allogeneic hematopoietic cell transplantation. Cytotherapy. 2020;22:21-26.

14.    Arndt C, Loureiro LR, Feldmann A, Jureczek J, Bergmann R, Mathe D, Hegedus N, Berndt N, Koristka S, Mitwasi N, Fasslrinner F, Lamprecht C, Kegler A, Hoffmann A, Bartsch T, Köseer AS, Egan G, Schmitz M, Horejsi V, Krause M, Dubrovska A, Bachmann M. UniCAR T cell immunotherapy enables efficient elimination of radioresistant cancer cells. Oncoimmunology. 2020;9:1743036.   

15.    Binnewerg B, Schubert M, Voronkina A, Muzychka L, Wysokowski M, Petrenko I, Djurovic M, Kovalchuk V, Tsurkan M, Martinovic R, Bechmann N, Fursov A, Ivanenko VN, Tabachnick KR, Smolii OB, Joseph Y, Giovine M, Bornstein SR, Stelling AL, Tunger A, Schmitz M, Taniya OS, Kovalev IS, Zyryanov GV, Guan K, Ehrlich H. Marine biomaterials: biometric and pharmacological potential of cultivated Aplysina aerophoba marine demosponge. Mater Sci Eng C Mater Biol Appl. 2020;109:110566.  

16.    Gellrich FF, Schmitz M, Beissert S, Meier F. Anti-PD-1 and novel combinations in the treatment of melanoma – An update. J Clin Med. 2020,9:223.

17.    Rammensee HG, Wiesmüller KH, Chandran PA, Zelba H, Rusch E, Gouttefangeas C, Kowalewski DJ, Di Marco M, Haen SP, Walz JS, Gloria YC, Bödder J, Schertel JM, Tunger A, Müller L, Kießler M, Wehner R, Schmitz M, Jakobi M, Schneiderhan-Marra N, Klein R, Laske K, Artzner K, Backert L, Schuster H, Schwenck J, Weber ANR, Pichler B, Kneilling M, la Fougère C, Forchhammer S, Metzler G, Bauer J, Weide B, Schippert W, Stevanović, Löffler MW. A new synthetic toll-like receptor 1/2 ligand is an efficient adjuvant for peptide vaccination in a human volunteer. J Immunother Cancer. 2019;7:307. 

18.    Tunger A, Sommer U, Wehner R, Kubasch AS, Grimm MO, Bachmann M, Platzbecker U, Bornhäuser M, Baretton G, Schmitz M. The evolving landscape of biomarkers for anti-PD-1 or anti PD-L1 therapy. J Clin Med. 2019,8:E1534. 

19.    Ahmad F, Döbel T, Schmitz M, Schäkel K. Current concepts of 6-sulfo LacNAc- expressing monocytes (slanMo). Front Immunol. 2019;10:948.

20.    Kegler A, Koristka S, Bergmann R, Berndt N, Arndt C, Feldmann A, Hoffmann A, Bornhäuser M, Schmitz M, Bachmann MP. T cells engrafted with a UniCAR 28/z outperform UniCAR BB/z-transduced T cells in the face of regulatory T cell-mediated immunosuppression. Oncoimmunology. 2019;7:e1621676.

21.    Adhikaree J, Franks HA, Televantos C, Vaghela P, Kaur AP, Walker D, Schmitz M, Jackson AM, Patel PM. Impaired circulating myeloid CD1c+ dendritic cell function in human glioblastoma is restored by p38 inhibition - implications for the next generation of DC vaccines. Oncoimmunology. 2019;8:1593803.

22.    Wagner F, Hölig U, Wilczkowski F, Plesca I, Sommer U, Wehner R, Maximilian Kießler M, Jarosch A, Flecke K, Arsova M, Tunger A, Bogner, Reißfelder C, Weitz J, Schäkel K, Troost EGC, Krause M, Folprecht G, Bornhäuser M, Bachmann MP, Aust D, Baretton G, Schmitz M. Neoadjuvant radiochemotherapy significantly alters the phenotype of plasmacytoid dendritic cells and 6-sulfo LacNAc+ monocytes in rectal cancer. Front Immunol. 2019;10:602. 

23.    Kuske M, Westphal D, Wehner R, Schmitz M, Beissert S, Praetorius C, Meier F. Immunomodulatory effects of BRAF and MEK inhibitors: implications for melanoma therapy. Pharmacol Res. 2018;136:151-159.

24.    Baran W, Oehrl S, Ahmad F, Döbel T, Alt C, Buske-Kirschbaum A, Schmitz M, Schäkel K. Phenotype, function and mobilization of 6-sulfo LacNAc-expressing monocytes in atopic dermatitis. Front Immunol. 2018;9:1352.

25.    Olaru F, Döbel T, Lonsdorf AS, Oehrl S, Maas M, Enk AH, Schmitz M, Gröne EF, Gröne HJ, Schäkel K. Intracapillary immune complexes recruit and activate slan-expressing CD16+ monocytes in human lupus nephritis. JCI Insight. 2018;3:e96492.

26.    Albert S, Arndt C, Koristka S, Berndt N, Bergmann R, Feldmann A, Schmitz M, Pietzsch J, Steinbach J, Bachmann M. From mono- to bivalent: improving theranostic properties of target modules for redirection of UniCAR T cells against EGFR-expressing tumor cells in vitro and in vivo. Oncotarget. 2018;9:25597-25616.

27.    Kubasch AS, Wehner R, Bazzuri S, Tunger A, Stasik S, Garzarolli M, Meinel J, Baretton G, Friedegund M, Thiede C, Schmitz M, Platzbecker U. Clinical, molecular and immunological responses to pembrolizumab treatment for synchronous melanoma and acute myeloid leukemia. Blood Adv. 2018;2:1187-1190.

28.    Matko S, Manderla J, Bonsack M, Schmitz M, Bornhauser M, Tonn T, Odendahl M. PRAME peptide-specific CD8+ T cells represent the predominant response against leukemia-associated antigens (LAAs) in healthy individuals. Eur J Immunol. 2018;48:1400-1411.

29.    Tunger A, Kießler M, Wehner R, Temme A, Meyer F, Bachmann M, Schmitz M. Immune monitoring of cancer patients prior and during CTLA-4 or PD1/PD-L1 inhibitor treatment. Biomedicines. 2018;6:26.

30.    Heidenreich F, Rücker-Braun E, Walz JS, Eugster A, Kühn D, Dietz S, Nelde A, Tunger A, Wehner R, Link CS, Middeke JM, Stölzel F, Tonn T, Stevanovic S, Rammensee HG, Bonifacio E, Bachmann M, Zeis M, Ehninger G, Bornhäuser M, Schetelig J, Schmitz M. Mass spectrometry-based identification of a naturally presented receptor tyrosine kinase-like orphan receptor 1-derived epitope recognized by CD8+ cytotoxic T cells. Haematologica. 2017;102:e460-e464.

31.    Oehrl S, Olaru F, Kunze A, Maas M, Pezer S, Schmitz M, Schäkel K. Controlling the pro-inflammatory function of 6-sulfo LacNAc (slan) dendritic cells with dimethylfumarate. J Dermatol Sci. 2017;87:278-284.

32.    Matko S, Teichert M, Tunger A, Schmitz M, Bornhauser M, Tonn T, Odendahl M. Enumeration of WT1-specific CD8+ T cells for clinical application using an MHC streptamer-based no-wash single-platform flow cytometric assay. Cytometry A. 2017;91:1001-1008.

33.    Albert S, Arndt C, Feldmann A, Bergmann R, Bachmann D, Koristka S, Ludwig F, Ziller-Walter P, Kegler A, Gärtner S, Schmitz M, Ehninger A, Cartellieri M, Ehninger G, Pietzsch HJ,  Pietzsch J, Steinbach J, Bachmann M. A novel nanobody-based target module for retargeting of T lymphocytes to EGFR-expressing cancer cells via the modular UniCAR platform. Oncoimmunology. 2017;6:e1287246.

34.    Feldmann A, Arndt C, Bergmann R, Loff S, Cartellieri M, Bachmann D, Aliperta R, Hetzenecker M, Ludwig F, Albert S, Ziller-Walter P, Kegler A, Koristka S, Gärtner S, Schmitz M, Ehninger A, Ehninger G, Pietzsch J, Steinbach J, Bachmann M. Retargeting of T lymphocytes to PSCA- or PSMA positive prostate cancer cells using the novel modular chimeric antigen receptor platform technology UniCAR. Oncotarget. 2017;8:31368-31385. 

35.    Tunger A, Wehner R, von Bonin M, Kühn D, Heidenreich F, Matko S, Nauerth M, Rücker-Braun E, Dietz S, Link CS, Eugster A, Odendahl M, Busch DH, Tonn T, Bonifacio E, Germeroth L, Schetelig J, Bachmann MP, Bornhäuser M, Schmitz M. Generation of high-avidity, WT1-reactive CD8+ cytotoxic T cell clones with anti-leukemic activity by streptamer technology. Leuk Lymphoma. 2017;58:1246-1249.

36.    Rücker-Braun E, Schetelig J, Link CS, Schmiedgen M, Tunger A, Vizjak P, Teipel R, Wehner R, Kuehn D, Fuchs YF, Oelschlaegel U, Germeroth L, Schmitz M, Bornhäuser M, Schetelig J, Heidenreich F. Longitudinal analyses of leukemia-associated antigen-specific CD8+ T cells in patients after allogeneic stem cell transplantation. Exp Hematol. 2016;44:1024-1033.

37.    Temme A, Schmitz M. Chimeric antigen receptor-engineered primary natural killer cells: a tool to improve adoptive tumor immunotherapy. Immunotherapy. 2016;8:983-986. 

 

 

Head

Prof. Dr. Marc Schmitz
Institute of Immunology, Medical Faculty Carl Gustav Carus, TU Dresden
Tel.: + 49 (0) 351 4586501
E-Mail: marc.schmitz(at)tu-dresden.de

Coordination

Dr. Rebekka Wehner
Institute of Immunology, Medical Faculty Carl Gustav Carus, TU Dresden
Tel.: + 49 (0) 351 45816524
E-Mail: rebekka.wehner(at)tu-dresden.de

Staff

Cathleen Lippitsch
NCT/UCC Dresden
Tel.: + 49 (0) 351 458 6514
E-Mail: cathleen.lippitsch(at)nct-dresden.de

Susanne Doms
NCT/UCC Dresden
Tel.: + 49 (0) 351 458 16528
susanne.doms(at)nct-dresden.de

Linda Alter
NCT/UCC Dresden
linda.alter(at)nct.dresden.de