Tumor Immunology meets Oncology: Insights from the TIMO XVIII Symposium

The convergence of immunology and oncology has paved the way for ground breaking advancements in cancer research and treatment. The recent Symposium Tumor Immunology meets Oncology XVIII (TIMO XVIII) at the Old Townhall in Brandenburg at the Havel, Germany, served once again as a nexus for leading scientists, clinicians and young researchers from 13 different countries to showcase their latest findings, exchange ideas and share insights.

TIMO XVIII was hosted by Prof. Dr. Barbara Seliger, director of the Institute for Translational Immunology at the Brandenburg Medical School. Seliger has witnessed and helped shape the development of immunotherapy from the very beginning, being director of the Institute for Medical Immunology at the Martin Luther University Halle-Wittenberg for 20 years.

Therapeutic potential of the extracellular matrix protein biglycan

Seliger opened the symposium with one of its key topics: the dynamic interplay between the tumor microenvironment and the immune system. Researchers at her institute are currently addressing the question, how extracellular matrix proteins regulate immune escape and immune surveillance mechanisms. In this context, Seliger sees great therapeutic potential for the small leucine rich protein biglycan. Overexpression of the tumor related HER-2/neu gene is inversely correlated with biglycan expression, for example.1 If the researchers increased the biglycan concentration in HER-2/neu+ cells, they were less tumorigenic in immune competent mice, while immune cell responses were enhanced and frequencies of immune effector cells in tumors and peripheral blood were increased.

Dr. Vincenzo Bronte from the University of Verona, Italy, presents his research focus after Prof. Seliger. Photo: Michael Hoetzel; DGPh
Dr. Vincenzo Bronte from the University of Verona, Italy, presents his research focus after Prof. Seliger.
Photo: Michael Hoetzel; DGPh

SOPRANO algorithm deciphers cancer's immune evasion tactics

In a large number of lectures the speakers then delved into diverse topics, ranging from the intricate mechanisms of immune evasion by cancer cells to strategies against an “unfriendly” tumor environment and poor response rates to immunotherapy.
Dr. Luis Zapata Ortiz from The Institute of Cancer Research, London, elucidated the role of the tumor immune landscape in predicting treatment outcomes. Together with his Evolutionary Immunogenomics team he has developed an algorithm that determines the type of immune evasion present in cancer cells. Zapata Ortiz and colleagues trained the SOPRANO-algorithm on genomic data from 10,000 cancer samples across 33 cancer types from the Cancer Genome Atlas. SOPRANO is now able to differentiate between cancer cells that merely cloak neoantigens and others that reduce the number of neoantigens on their surface. As immunotherapy removes the ‘cloak’ on cancer cells, patients with this kind of immune evasion will respond to immune checkpoint inhibitor therapies. Zapata Ortiz and colleagues also hope to identify at what point initial cloaking triggers the development of cancer. This would help to detect cancer earlier and therefore target it at its most treatable.

 

Non-canonical peptides as promising targets across tumor types

In the very last lecture of the symposium, Bernard A. Fox addressed the exciting field of non-canonical peptides, which have only been detected on cancer cells in the last three years.2 Fox leads the Laboratory of Molecular and Tumor Immunology at the Earle A. Chiles Research Institute in Portland, USA, and is the Founder and CEO of UbiVac. Non-canonical peptides are aberrantly translated proteins derived from upstream open reading frames, 5′UTRs, ncRNAs, endogenous retroelements, pseudogenes and out-of-frame transcripts. Most of the non-canonical peptides are short-lived proteins or defective ribosomal products that are typically degraded within 30 minutes. Since they were not subjects to thymic selection, they are efficiently captured by MHC class I molecules. Therefore, they are widely distributed on the surface of tumor cells, but endogenous tumor-reactive T cells do not respond to them.

Bernard A. Fox presents the noncanonical peptides.

Bernard A. Fox presents the noncanonical peptides.

However, in vitro sensitization of donor peripheral blood lymphocytes against non-canonical tumor HLA-I ligands led to the identification of ligand-specific T cell receptors. Such sensitized T cells recognized cancer cell lines naturally presenting their corresponding antigens.
The targeted non-canonical peptides are expressed across tumor types – including endometrial, ovarian and gastrointestinal carcinoma as well as melanoma, but are barely or not at all detectable in normal cells. Such insights hold immense promise for the development of personalized immunotherapies.

 

TIMO XVIII lectures sparked productive discussions

The TIMO XVIII Symposium presented a comprehensive picture of current research on the intricate interplay between the immune system and cancer as well as on the development of novel immune therapeutic strategies. It also showed how bioinformatics-based artificial intelligence approaches can enhance the efficacy of (immuno)therapies and help develop individually tailored treatments. This sparked productive discussions about additional research avenues after the lectures, during coffee breaks, at the poster session and the cheerful evening reception. By bringing these ideas back to the lab, symposium participants helped the research community and clinicians move one step closer to its ultimate goal: to effectively harness the power of the immune system to defeat cancer.

The symposium participants from 13 different countries. Photo: Michael Hoetzel; DGPh

The symposium participants from 13 different countries.
Photo: Michael Hoetzel; DGPh

Publications:

1. Subbarayan, Karthikeyan et al. “Biglycan-mediated upregulation of MHC class I expression in HER-2/neu-transformed cells.” Oncoimmunology vol. 7,4 e1373233. 16 Jan. 2018, doi:10.1080/2162402X.2017.1373233 
2. Fox, Bernard A et al. “Cancer's Dark Matter: Lighting the Abyss Unveils Universe of New Therapies.” Clinical cancer research: an official journal of the American Association for Cancer Research vol. 29,12 (2023): 2173-2175. doi:10.1158/1078-0432.CCR-23-0422

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