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ICML 2025 | Using LBCL LymphoMAPs to identify subgroups of patients who benefit from CAR T-cell therapy
Stephen Ansell, MD, PhD, Mayo Clinic, Rochester, MN, comments on the use of LymphoMAPs to identify subgroups of patients with large B-cell lymphoma (LBCL) who derive benefit from CAR T-cell therapy. Prof. Ansell highlights that patients with a lymph node microenvironment resembling a normal lymph node tend to respond well to immunotherapeutic approaches, while those with exhausted T-cells or a fibroblast and macrophage-rich microenvironment respond poorly. This interview took place during the 18th International Conference on Malignant Lymphoma (18-ICML) in Lugano, Switzerland.
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Transcript
Very interesting data has shown that in the microenvironment or the area around the tumor cells in large cell lymphoma, there are different patterns or archetypes called LymphoMAPs in this case that can be identified, and really three things were noted. One pattern that looks like more of a normal lymph node, a second pattern that shows lots of T-cells but those T-cells have an exhausted phenotype, and the third pattern, which shows very few T-cells but has a lot of fibroblasts and macrophages...
Very interesting data has shown that in the microenvironment or the area around the tumor cells in large cell lymphoma, there are different patterns or archetypes called LymphoMAPs in this case that can be identified, and really three things were noted. One pattern that looks like more of a normal lymph node, a second pattern that shows lots of T-cells but those T-cells have an exhausted phenotype, and the third pattern, which shows very few T-cells but has a lot of fibroblasts and macrophages. And so, when looking at those three patterns, the biggest thing that was noted was patients that have this more normal-looking environment, the lymph node environment, those patients do very well with immunotherapies, particularly CAR T-cell treatment. The other patients don’t do particularly well and have a very similar kind of response to what is seen with chemotherapy.
So, I think what we’re learning from that is that the more normal the microenvironment, the greater the microenvironment can respond to treatment like cellular therapies, CAR T-cell treatments. And I think the second thing that we learned was that certain cytokines, TGF-beta, gamma interferon, really seem to activate the environment and, by doing so, actually over-activate it and make it more exhausted, and in that case, may actually take it from a good environment to a bad one. So, that’s a second target that we might be able to look at.
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