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.

KEYWORDS
human cohorts, immunotherapy, mouse models, skin cancer, tertiary lymphoid structures

Histological analysis of TLS in melanoma patients. (A) TLS were quantified in biopsies of melanoma patients after treatment with T-VEC and compared in responders (R, n=2, 3 slides per patient) and non-responders (NR, n=2, two slides per patient) by Students t-test with Welch's correction. Only responders had GC+ TLS. (B) Representative image of a T-VEC responder with many peritumoral TLS (black arrowheads).
Histological analysis of TLS in melanoma patients. (A) TLS were quantified in biopsies of melanoma patients after treatment with T-VEC and compared in responders (R, n=2, 3 slides per patient) and non-responders (NR, n=2, two slides per patient) by Students t-test with Welch's correction. Only responders had GC+ TLS. (B) Representative image of a T-VEC responder with many peritumoral TLS (black arrowheads).
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.

 
Prof. Maries van den Broek


Prof. Maries van den Broek
University of Zurich
Institute of Experimental Immunology
Winterthurerstrasse 190
8057 Zurich

Email   Website

Selected publications

SKINTEGRITY.CH Principal Investigators are in bold:

  • Pagliarulo F, Cheng P, Brugger L, van Dijk N, van der Heijden M, Levesque M, Silina K, van den Broek M (2022). Molecular, immunological, and clinical features associated with lymphoid neogenesis in muscle invasive bladder cancer. Front Immunol, 12:793992.
  • Van Dijk N, Gil-Jimenz A, Silina K, van Montfoort M, Einerhand S, Jonkman L, Voskuilen C, Peters D, Sanders J, Lubeck Y, Broeks A, Hooijberg E, Vis D, van den Broek M, Wessels L, van Rhijn B and van der Heijden M (2022). The tumor immune landscape and architecture of tertiary lymphoid structures in urothelial cancer. Front Immunol, 12:793964.
  • Tallón de Lara P, Castañón Cuadrado H, Vermeer M, Núñez N, Silina K, Sobottka B, Urdínez J, Cecconi V, Yagita H, Movahedian Attar F, Hiltbrunner S, Glarner I, Moch H, Tugues S, Becher B and van den Broek M (2021). CD39+PD-1+CD8+ T-cells mediate metastatic dormancy in breast cancer. Nat Commun, 12(1), p. 769.
  • Lelios I, Stifter SA, Cecconi V, Petrova E, Lutz M, Cansever D, Utz SG, Becher B and van den Broek M, Greter M (2021). Monocytes promote UV-induced epidermal carcinogenesis. Eur J Imunol, 51(7), pp. 1799-1808.
  • Sobottka B, Lorch A, Silina K, van den Broek M, and Moch H. (2021). Renal cell carcinoma pathology in 2021: New need for renal cancer immune profiling. Curr Opin Urol, 31(3), pp. 228-235.