Human cohorts, Immunotherapy, Mouse models, Skin cancer, Tertiary lymphoid structures
What we investigate
We aim to better understand the mutual interaction between the immune system and cancer, and how therapeutic interventions change these interactions. This knowledge will contribute to development of novel therapies for cancer that optimally engage the body’s own defense system.
Our research in more detail
The tumor microenvironment (TME) has a substantial influence on disease progression and response to therapy. Recently, tertiary lymphoid structures (TLS) were recognized as a relevant immune component of the TME. In cancer patients, TLS correlate with improved survival in a growing list of tumor types, suggesting that TLS contribute to anti-tumor immunity. Along the same lines, TLS density may have predictive potential for the clinical response to immunotherapy.
Immune checkpoint inhibition results in significant and durable clinical responses in a proportion of cancer patients but is ineffective in others. Predicting which patients will benefit from this treatment and/or develop severe toxicity is still a challenge, and data regarding predictive biomarkers are conflicting.
We propose here that the immune composition of the TME including the presence of TLS influences the efficacy of immune checkpoint inhibition.
To test this hypothesis, we will use samples from cohorts of patients with skin cancer as well as preclinical models for cancer and TLS-induction. Specifically, we will use state-of-the-art technologies such as multispectral immunofluorescence imaging allowing high-dimensional analysis of the TME while maintaining the spatial context.
SKINTEGRITY.CH Principal Investigators are underlined:
- Silina K, Soltermann A, Movahedian Attar F, Casanova R, Uckeley Z, Thut H, Isajevs S, Cheng S, Curioni-Fontecedro A, Foukas P, Levesque M, Moch H, Linē A, van den Broek M (2018). Germinal centers determine the prognostic relevance of tertiary lymphoid structures and are impaired by corticosteroids in lung squamous cell carcinoma. Cancer Res 78:1308-1320.
- Posch F, Silina K, Leibl S, Mündlein A, Moch H, Siebenhüner A, Pestalozzi B, Riedl J, Stotz M, Szkandera J, Stöger H, Pichler M, Stupp R, van den Broek M, Schraml P, Gerger A, Petrausch U, Winder T (2017). Maturation of tertiary lymphoid structures predicts the risk for recurrence in stage II and III colorectal cancer. OncoImmunology 7: e1378844.
- Silina K., Burkhardt C., Casanova R., Solterman A., van den Broek M (2018). A Quantitative Pathology Approach to Analyze the Development of Human Cancer-Associated Tertiary Lymphoid Structures. In: Dieu-Nosjean MC. (eds) Tertiary Lymphoid Structures. Methods in Molecular Biology, vol 1845. Humana Press, New York, NY.
- Tallón de Lara P, Castañón Cuadrado H, Vermeer M, Núñez N, Silina K, Sobottka B, Urdínez J, Cecconi V, Movahedian Attar F, Hiltbrunner S, Glarner I, Moch H, Tugues S, Becher B, van den Broek M (2020). CD39+PD-1+CD8+ T-cells mediate metastatic dormancy in breast cancer. BioRxiv https://doi.org/10.1101/2020.06.02.126037.