Interested in Immune regulation, big data modelling, and networking?

Immunology is such an exciting field – in recent years, tons of new developments and theories have sprung up like mushrooms after rain. Interestingly, just as there are different trends in the fashion world, scientific research also has different hotspots every year. Various annual international scientific conferences certainly provide the stage for current research trends in Immunology. One of the high-level meetings is the European Congress of Immunology (ECI), which just dropped its 5th curtain down in Amsterdam in September 2018. I was very excited to witness the immunological front-lines, ranging from immune checkpoint cancer therapy, and big data modelling, to modulate functions of extracellular vesicles.

Chun-Feng Yu in Amsterdam (image by C. Yu)

ECI 2018 was first opened with the keynote lecture from Dr. Tasuku Honjo (Kyoto University Japan), who summarized his intense and extraordinary research on PD-1 immune checkpoint blockade in Cancer Immunotherapy. The knowledge in the speech was so important and exciting that Dr. Honjo was awarded jointly with Dr. James P. Allison with the Nobel Prize in Medicine one month later due to “their discovery of cancer therapy by inhibition of negative immune regulation”. If you are interested in this topic, I suggest the brief introductions elaborating the use of brake mechanism of PD-1 and CTLA-4 in T cell immune responses against tumor posted by Dr. Isis Ludwig-Portugall and Julia Reinhardt on their blogs earlier. The two Nobel laureates have established a novel strategy to unleash the inherent immune system to attack cancer by blocking the inhibitory function of checkpoint molecules. Without a doubt, immune checkpoint cancer therapy is a milestone in tumor treatment, mirrored by its striking therapeutic effects in clinical studies. The blockage of CTLA-4 enhances immune responses against immunogenic tumors such as lymphoma. In comparison, single agent with PD-1 blockade has a more effective therapeutic potential against poorly immunogenic tumors and a lower toxicity in clinical trials than anti- CTLA-4 therapy (1, 2). Nivolumab, a human IgG4 anti-PD-1 monoclonal therapeutical antibody, achieved 72.9% overall survival of one year in advanced melanoma patients. Nivolumab treatment demonstrates 18% and 27% response rate in patients with non-small cell lung cancer and renal cell carcinoma individually. Together, anti-PD-1 therapy has been effective in more than 25 different types of solid tumors and several hematopoietic malignancies, and achieved FDA approval in treatment against 12 types of cancer (3). Foreseeably, immune checkpoint cancer therapy will draw more attention worldwide in fighting cancer and encourages studies searching for new checkpoint proteins.

The research on exosomes, one type of extracellular vesicles, with diameter in the range of 30–150 nm, represents another dramatically booming field in Immunology (4). Exosomes are derived from endosomal multivesicular bodies (MVB) when the MVB fuses with the plasma membrane and gets released into the extracellular environment. Since they serve as a communication tool between cells and in the transmission of disease states, there is an exploration of interest on exosomes in the last few years (4,5). There were plenty of conference posters and talks describing the molecular composition and biological functions of extracellular vesicles both in health and disease. Indeed, exosomes contain promising biomarkers which are essential for disease diagnosis, especially for certain cancer early diagnosis, although at present purification and characterization of the extremely tiny vesicles is a big challenge due to the lackage of exclusive markers. By delivering their molecular cargo including cytokines, lipids, nucleic RNA, DNA, and enzymes, exosomes play essential roles in acute and chronic inflammation, as well as autoimmune diseases. A talk given by Dr. Gabrielsson (Karolinska Institutet, Sweden) demonstrated that exosomes released by allogeneic dendritic cells induced robust T cell responses in a B16 melanoma model that highlighted the perspective of exosome-based immunotherapy.

The conference motto was ”build bridges”, thus, system geneticist and bioinformatician Dr. Li (University of Groningen, Netherlands) and Dr. Westerhoff (AIMMS and SILS and MCISB, Netherlands) were invited to lead one workshop titled “Deep Thing in Immunology”. The immune system is one of the most complex systems, which involves temporal and spatial regulation of more than 75,000 immune molecules. To understand the complicated networks of those molecules and the connection of their biological functions with human diseases, immunologists now have to befriend computer and system biology to integrate the huge mass of experimental data into deep mathematical models for better understanding and prediction of human diseases. Deep thinking with the help of modeling softwares will empower our observation and imagination close to immunological reality. Moreover, the lecture by Dr. Westerhoff explained how the established model based on big experimental data promoted the understanding of the difference between acute and chronic inflammation.

Although it was already in the night when I came out of the conference venue, I was really excited about the progress of immunology this year. I am so happy that I took part in this high-level immunological conference, which updates my knowledge of the frontier research and gives me a chance to communicate with scientists with sparkling ideas.

It was great to meet our UKB administration team of ImmunoSensation at the ECI 2018, which offers extraordinary research exchange programs worldwide for PhD students and postdocs. Here, I would like to greatly appreciate the interdisciplinary platform of ImmunoSensation, which connects classical Immunology with other sciences, including System Biology, Neuroscience, and Genetics, and recruits over 20 excellent research groups from the University of Bonn, CAESAR, and DZNE. The valuable collaboration in technology, ideas, and material sharing has greatly helped our projects. Moreover, seminars, workshops, and public activities offered by ImmunoSensation widely broaden my views in Immunology.

The immune system is an amazing complex biological micro-ecosystem of innate and adaptive, highly diversified and self-organized immune cells that collaborate. Luckily, we experience a new era, where scientists from different fields are working together to understand the system and deal with immune disorders. I think we will understand our immune system even more deeply in a few decades. At this point, I am quite optimistic. Just as mentioned by the Nobel laureate Dr. James P. Allison, “Science is a long and frustrating road… You’ve got to be comfortable with a lot of failures to get there.”

References:

  1. Cancer immunotherapies targeting the PD-1 signaling pathway. (2017). Iwai Y et al. J Biomed Sci. 24: 26.
  2. A Paradigm Shift in Cancer Immunotherapy: From Enhancement to Normalization. Sanmamed MF et al. (2018).  Cell.175: 13-326.
  3. Cancer immunotherapy using checkpoint blockade. (2018). Ribas, A et al.  Science 359: 1350-1355.
  4. Q&A: What are exosomes, exactly? (2016). Edgar JR. BMC Biol. 14:46.
  5. Exosomes in inflammation and role as biomarkers. (2018). Console L et al. Clin Chim Acta. 488:165-171.

Chun-Feng Yu

(featured image from colourbox.com/Neirfy)

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