iwNHL 2025 | The potential role of spatial transcriptomics and liquid biopsy in DLBCL

So those are all very active areas of investigation in diffuse large B-cell lymphoma right now. So one of the ways that you could envision ctDNA, which I think has already begun to be incorporated into diffuse large B-cell lymphoma, is you could think about the ctDNA analysis essentially as an aggregate of what you might see if you did biopsies of multiple different sites of involvement. So what you have in the ctDNA is you have an aggregate of that genetic signature, so it may be more accurate. The other thing that’s really advantageous about ctDNA is that it allows you, because it’s a simple blood test, to serially monitor that over time. And so you can look at that at baseline and then at a midpoint during therapy and then at the end of therapy, and to the extent that you can take a molecular aggregate of that information, you can look to see if a patient has actually cleared tumor, and that is an important treatment endpoint. And so that’s particularly advantageous. 

And then with regard to spatial transcriptomics, part of the reason that that’s a very active and interesting area of investigation is that immunotherapies right now, particularly CAR T-cells and bispecific antibodies, are particularly effective in diffuse large B-cell lymphoma. And so it really says that there’s likely to be a very important role in modulating mechanisms of immune evasion and augmenting an immune response to the tumor as a therapeutic approach in the disease. And so understanding then the intact tumor microenvironment and understanding what the different composition of the immune cells is in the intact tumor microenvironment in a disease like diffuse large B-cell lymphoma will be very important in terms of understanding how it is that these immunotherapies might work best. And it will also be important because we think that there are likely to be some places where the genetic signature in diffuse large B-cell lymphoma is related to what you actually see in terms of the cellular composition in the intact tumor microenvironment. So understanding the ways that those pieces of information relate to each other and also the ways in which the information that’s identified by spatial transcriptomics provides an additional layer of information in DLBCL is going to be very important.

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