ESMO 2025 | Novel management strategies for melanoma beyond checkpoint inhibitors
Ines Pires da Silva, MD, PhD, Melanoma Institute Australia, Sydney, Australia, highlights the challenges of resistance to immunotherapy in melanoma and the need to divide patients into responsive, resistant, and potentially responsive groups based on various factors. Novel strategies, such as personalized vaccines, immunomodulatory vaccines, and cellular therapies like tumor infiltrating lymphocytes (TILs), TCR T cells, and CAR T cells, may help overcome resistance, but biomarkers will be essential to select the right patients for these treatments. This interview took place at the European Society for Medical Oncology (ESMO) 2025 Congress in Berlin, Germany.
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Transcript
Once we have resistance to immunotherapy, several, or immune checkpoints, let’s say this way, several features play into here. So we have things related to the host, with a tumor, and I gave an educational session on that, covering several things. I guess this is a very tricky question, because in my opinion, we have, and we have data already, there are the responsive patients, right? Those patients, independent of other features, they respond...
Once we have resistance to immunotherapy, several, or immune checkpoints, let’s say this way, several features play into here. So we have things related to the host, with a tumor, and I gave an educational session on that, covering several things. I guess this is a very tricky question, because in my opinion, we have, and we have data already, there are the responsive patients, right? Those patients, independent of other features, they respond. We have the resistant patients that even if we modulate probably the gut microbiome or the time, the chronotherapy that’s now been discussed, even if we do that, they are still resistant, right? So I guess what we have to now start to divide patients into are the responsive patients, the resistant patients, and the ones in the middle that they might be responsive if we modulate those things, right? But I think your question goes beyond that. How can we tackle those resistant patients? Well, if we needed the answer, we wouldn’t be here, right? But from my perspective, we have novel strategies in terms of immunotherapy. Of course, we have to use, again, biomarkers to select those patients. They tend to be a bit more, probably, tricky techniques and drugs to treat with. Might be more toxic, some of them, not necessarily. So I’ll probably highlight the personalized vaccines, but not only personalized. So I’m going to talk about the immunomodulatory. There’s an oral presentation here about immunomodulatory vaccine. That’s a very interesting concept. And those are not toxic at all. So that’s one of the ways to probably overcome resistance, even though that trial was not in that setting. We have TILs and all the cellular therapies. So TCR T cells, CAR T cells, of course, all of them, they have their limitations, some of them they only target one antigen, some target multiple antigens, but I think what we have to do is to identify the resistant patients and be smart and try to treat those specific patients with these novel technologies and try to get better.
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