The conference at Lorne in Victoria, Australia of the “27th Lorne Cancer Conference” was a general cancer conference with a focus on melanoma, due to the extremely high incidence of this disease in the Australian population.
The poster presentation that I gave, “Oxidative burst produced by the NOX2 complex does not play a role in methylcholanthrene induced sarcoma development”, had a very specific audience in a conference covering such generic cancer and cancer therapies, nonetheless the couple of interested parties were engaged in lively discussion that endured the entire evening. Regardless of the broad nature of the conference there were three recurring themes at this conference: Below I will summarize a couple of the interesting topics that were covered by multiple speakers:
(I) Immunotherapy was the big hit topic at this conference. Around 50% of the talks were centered on immunology. Highlighting the shift in the cancer treatment field with regards to the implications cancer therapy. Of course the very popular PD1-PDL1 checkpoint blockade antibody was much discussed. But many difficulties remain in identifying which patients will be responders leading to the newest rage of combination therapy. Willem J Lesterhuis spoke about an interesting new method to identify potential combination therapies. By injecting a mouse on both flanks with a tumor, treating with CTLA-4 antibody, followed by removal of one tumor and screening the signatures of these tumors. By comparing responders to non-responders and performing network analysis they were able to identify drugs that would be able to enhance these pathways in non-responders. This increased the cure rate from 10% to 80% by administration of re-purposed approved drugs. In another immunotherapeutic vein vaccination against cancer is still alive and kicking. NKT cells have long been recognized to be strong inflammatory activators of the immune system. Steve Mattarollo decided to active these cells in combination with the delivery of irradiated tumor cells loaded with alpha-Gal. This elicited a potentate therapeutic immune response against non-Hodgkin’s lymphoma that was CD8 T cell mediated.
(II) Small molecule inhibitors remain a hot topic. Identifying driver-mutations as potential future targets for therapy requires the extensive genomic mapping that Nick Hayward and the Australian Melanoma Genome Project are undertaking with International Cancer Genome Consortium. He also showed that they were screening for the methylation signatures as well as protein phosphorylation signature from their melanoma samples. This provides important databases for improving targeted therapy. Yardena Samuels joins the ranks of researchers digging for mutations that play a role in driving tumorigenesis. But contrary to many of her colleagues she has found an interesting mutation that is a synonymous somatic mutation in BCL2L12. This mutation does not alter the protein in any manner but directly leads to increased mRNA expression of this oncogene. Leading to oncogene addiction in the tumors that have this mutation and of course giving oncologists a potential new way to target these tumors.
(III) Fundamental tumor biology and in particular tumor-immunology drew much attention as well. Particularly interest in melanoma development and the role of UV irradiation. This has been Thomas Tuetings main point of research interest using in particular an interesting UV-sensitive Hgf-cdk4 melanoma mouse model they were able to show that neutrophils infiltrating UV damaged skin was a key driver in the development of the tumors. As well as driving tumorigenesis locally, neutrophils facilitated metastatic spread of the melanomas. With the success of immunotherapy in melanoma being so evident, Sherene Loi has devoted much of her time to studying in patients with breast cancer whether this is an other disease potentially treatable with immunotherapy. She was able to find much data that supported that even patients with triple negative breast cancer had a much-improved survival with increased immune cell infiltration. Additionally she was able to identify denovo-lymphoid structures that indicated that breast cancers could be strongly infiltrated. But disappointingly, and in contrast to the recent Brown et al 2014 immunogenic-antigen publication, mutations were not predictive for patients with Her2+ breast cancer tumor infiltrating lymphocytes. Though she hinted at there still being a window for combination therapy with Map kinase inhibitors and PD1 antibodies.
The Lorne cancer conference surprised me with the wide range of researchers that all seem to slowly be circling the field of cancer immunotherapy for new approaches to treat their patients. This is very promising for us here at the Karolinska that have such a strong group of researchers spearheading the effort to bringing this type of therapy to the clinics.
I would very much like to thank the Radiumhemmets Forskningsdfonder for supporting us with this travel grant.