Clinical significance of the local and systemic immunologic microenvironment in patients with colorectal cancer liver metastases
Final Report Abstract
In summary, our work has elucidated the complex role of immune responses in metastatic colorectal cancer. Within the tumor tissue of metastatic colorectal cancer, a specific exploitive immunological pathomechanism was identified, based on in-depth analyses of immune cells and cytokines within the tissue sub-compartments. In this situation, we decided to characterize the tissue more deeply and to embark on a clinical trial in order to validate our findings. The identified tissue characteristics together with a newly developed tissue explant model system allowed us to generate a successful clinical translation. This clinical translation leads to more clinical investigations and subsequent clinical trials are planned. Furthermore, the prominent publication of our findings resulted in more collaborative projects, leading to a better understanding of the immunological microenvironment in cancer. The role of tumor associated antigen specific antibodies in colorectal cancer patients was also addressed in parallel. There, specific patterns of responses could be identified and these patterns are currently corroborated in a larger second cohort of patients. Data coming from these analyses show specific patterns, where the integrative database that is being compiled currently will clearly allow to link serum with tissue in these patients. Further work is needed, but the easy access to patient serum is interesting for future applications in order to better stratify and treat patients.
Publications
- Hepatic metastases of colorectal cancer are rather homogeneous but differ from primary lesions in terms of immune cell infiltration. Oncoimmunology e24116 (2013)
Halama N, Spille A, Lerchl T, Brand K, Herpel E, Welte S, Keim S, Lahrmann B, Klupp F, Kahlert C, Weitz J, Grabe N, Jaeger D, Zoernig I
(See online at https://doi.org/10.4161/onci.24116) - Prognostic significance of spontaneous antibody responses against tumor-associated antigens in malignant melanoma patients. Int J Cancer 1:138-51 (2014)
Zörnig I, Halama N, Lorenzo Bermejo J, Ziegelmeier C, Dickes E, Migdoll A, Kaiser I, Waterboer T, Pawlita M, Grabe N, Ugurel S, Schadendorf D, Falk C, Eichmüller SB, Jäger D
(See online at https://doi.org/10.1002/ijc.28980) - Tumor-specific cytotoxic T lymphocyte activity determines colorectal cancer patient prognosis. J Clin Invest. 2015 2:739-751 (2015)
Reissfelder C, Stamova S, Gossmann C, Braun M, Bonertz A, Walliczek U, Grimm M, Rahbari NN, Koch M, Saadati M, Benner A, Büchler MW, Jäger D, Halama N, Khazaie K, Weitz J, Beckhove P
(See online at https://doi.org/10.1172/JCI74894) - Immunotherapy in gastrointestinal cancer: Recent results, current studies and future perspectives. Eur J Cancer. 59:160-70 (2016)
Moehler M, Delic M, Goepfert K, Aust D, Grabsch HI, Halama N, Heinrich B, Julie C, Lordick F, Lutz MP, Mauer M, Alsina Maqueda M, Schild H, Schimanski CC, Wagner AD, Roth A, Ducreux M
(See online at https://doi.org/10.1016/j.ejca.2016.02.020) - Immunotherapy of Colorectal Cancer. Oncol Res Treat. 6:346-50 (2016)
Jäger D, Halama N, Zörnig I, Klug P, Krauss J, Haag GM
(See online at https://doi.org/10.1159/000446713) - Tumoral Immune Cell Exploitation in Colorectal Cancer Metastases Can Be Targeted Effectively by Anti-CCR5 Therapy in Cancer Patients. Cancer Cell 4:587-601 (2016)
Halama N, Zoernig I, Berthel A, Kahlert C, Klupp F, Suarez-Carmona M, Suetterlin T, Brand K, Krauss J, Lasitschka F, Lerchl T, Luckner-Minden C, Ulrich A, Koch M, Weitz J, Schneider M, Buechler MW, Zitvogel L, Herrmann T, Benner A, Kunz C, Luecke S, Springfeld C, Grabe N, Falk CS, Jaeger D
(See online at https://doi.org/10.1016/j.ccell.2016.03.005) - Detailed resolution analysis reveals spatial T cell heterogeneity in the invasive margin of colorectal cancer liver metastases associated with improved survival. Oncoimmunology 3:e1286436 (2017)
Berthel A, Zoernig I, Valous NA, Kahlert C, Klupp F, Ulrich A, Weitz J, Jaeger D, Halama N
(See online at https://doi.org/10.1080/2162402X.2017.1286436)
