ESMO Immuno-Oncology 2025 | B-cell responses and tertiary lymphoid structures in endometrial cancer

Well, this is quite a new field we are entering down here. So we do know from wonderful papers in cancer in general that the B-cell system does play a role, more than we thought of in the beginning. I mean, a lot of attention within everything that’s going on in the field of immunology is the T cells and whatever they do are attracting a lot of attention, which is not fair to the B cell component, which is doing a lot of work in itself as well. So we already showed that within endometrial cancer, certainly within the MMRD, you find astonishing amounts of tertiary lymphoid structures, as we call them. More or less, you could say small lymph nodes, but then not only within the genome, but in the case of endometrial cancer, also in the myometrium of the uterus. And not only that, but within these tertiary lymphoid structures, you find everything you will find in a normal lymph node as well. So developing your B-cell component as well within two plasma blasts and producing antibodies. With a huge number of patients, we already have shown that the moment you have a strong B cell response in that field. Is it strong and acting on the T? Is it as strong acting on the B cell component? Yeah, more or less that are questions which still need to be answered and which I’m sure of will get a lot of answers the moment we are going to use more and more neoadjuvant checkpoint inhibitors because then you have the unique opportunity to study the tumor in detail after you have given your neoadjuvant drugs. To be honest, the uniqueness is also because within the trial we did, we gave two courses. Two courses is not enough to eradicate the tumor. We published on that in Nature Communications. You do see tremendous responses. You do see amazing work going on within the tumor the moment you have given two courses. But if you give pembrolizumab on its own or a checkpoint inhibitor on its own and not combined with ipilimumab, which has been done within rectal cancer, for instance, you might assume that there is still quite some tumor left the moment you go for surgery at that moment. And that gives the opportunity to study in detail what is really going on. So perfect question to ask, but I think we are going to learn within the next couple of months, years, what the real role of T versus B cell will be in neo-adjuvant specifically, but in IO in general.

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