The 2018 AACR annual meeting took place at McCormick Place in Chicago between April 14 and April 18. It was, without a doubt the largest conference that I have ever attended. About 25000 people attended this conference in a multidisciplinary environment that spanned all aspects of cancer research, from basic science to clinical trials and epidemiological studies. The conference included 11 plenary sessions, a broad number of symposia, educational sessions, methods workshops, meet the expert sessions, poster sessions, and a career fair.
GENERAL CONFERENCE DETAILS OF INTEREST:
Due to the size of the conference, it is essential to plan ahead what talks and sessions one is interested in attending. The best tool for this is the official app that is available on different platforms. Without it, navigating the conference and making an efficient use of my time there would have been impossible. Additionally, I didnt appreciate the fact that poster sessions were simultaneous with the talks. This makes it difficult to properly enjoy both of them. Finally, Id like to mention that the exhibitors area was humongous and it is worth a while taking a look at, especially the big lab providers, since it is always useful to interact with technical specialists that can answer detailed questions and provide support for their reagents and equipment.
Immunotherapy has taken the lead in cancer research: In the 11 plenary sessions, 9 were focused on immunology related topics, including three out of five talks in the opening plenary session. The most discussed topic was PD-1/PD-L1 blockade; how to predict responses, the mechanisms that underlie response/relapse to treatment and the possibilities of combination therapies with checkpoint blockade. Additionally, the next generation sequencing revolution has provided tools for sequencing the tumors (providing access to neoantigen information) and T and B cell repertoires of patients (providing information on the immune side of the story).
I presented a poster with our preliminary results monitoring the immune system of patients treated with the PD-1 blocking antibodies nivolumab and pembrolizumab. In this work, we showed that high frequencies of NK cells and low frequencies of monocytic MDSCs can be predictive biomarkers for treatment. These data attracted the attention of a broad spectrum of people, both working in the pharmaceutical industry and in academia. The four hour poster session, albeit tiring, somehow felt short as the interactions were uninterrupted.
Within the broad number of tumor immunology and immunotherapy talks I would like to highlight a few:
Padmanee Sharma, from MD Anderson presented her approach to rethink the current clinical trial paradigm, in what she called Reverse translational research. This consists in generating hypothesis in Phase I (II) trials and do lab interrogation in tissues or animal models to do analyses for biomarkers and test these hypothesis. In this framework, she presented interesting candidates for combining PD-1 antibodies. Along with her previous work with ICOS activating antibodies, she showed promising results blocking VISTA and CD47 in mouse macrophages. Currently there are ongoing safety trials with the VISTA antibodies.
Mark Davis (Stanford) gave a beautiful talk in which he presented a new algorithm (GLIPH) which showed the potential of predicting what antigens a TCR could recognize based on its sequence alone. In the field of cancer this could be extremely useful for personalized vaccine design, especially when coupled with PLGA nanoparticles as innate immune stimulators to awaken T cells. The results he presented looked very promising in B16F10 and MC38 mouse models.
Toni Ribas (UCLA), spoke about the importance of IFN signaling pathways in the antigen presentation machinery. He showed data that points out mutations in the JAK pathway as critical in patients who relapse after initial responses to PD-1 blockade. This highglights again the importance of combining PD-1 blockade with additional therapies that may target these pathways. He also highlighted the importance of harnessing the power of the innate immune response with either oncolytic viruses or TLR agonists that would increase tumor infiltration and improve the efficacy of checkpoint inhibitors.
In this line of work, Mohammed Milhem (Holden Comprehensive Cancer Center) presented the results from a phase 1b trial in which intratumoral injections of CMP-001, a CpG-A TLR9 agonist that is encapsulated in a virus-like particle, were given in combination with pembrolizumab to patients who had developed resistance to PD-1 blockade. The idea behind this combination is that the CpG-A stimulates TLR9 in pDCs, promoting the secretion of type I interferons and inflammatory chemokines, promoting T cell infiltration and rendering a ”cold” tumor into an immunologically ”hot” one, increasing the possibility of response to PD-1 blockade with pembrolizumab. The results were promising, showing two complete responses and 15 partial responses out of 69 patients.
Finally, I would like to highlight one poster which provided answers to some questions that we had regarding our work finding biomarkers in PD-1 blockade treated patients. This poster was presented by Jessica M. Sierra from the IBYME-CONICET in Buenos Aires, Argentina. In this poster they showed that NK cells are activated after being in contact with the tumor cell line K562 and that they upregulate PD-L1, changing their phenotype into ”regulatory” NK cells which are capable of suppressing T cells via the PD1/PD-L1 pathway. This contact has given me new ideas for phenotyping our patient cohort as well as new functional assays that we can perform with our biobanked material in order to understand the mechanisms that can connect NK cells to a successful response to checkpoint blockade.
Altogether, it was a great experience in a remarkable setting. I would like to thank Radiumhemmets Forskningsfonder for the finantial support I received that enabled me to attend this conference.