Joana Rodrigues, PhD student, Department of Immunotechnology, Lund University, Sweden, highlights an analysis exploring CD163-positive cells and their impact on the mantle cell lymphoma (MCL) microenvironment. The findings from this analysis were presented at the 2022 American Association for Cancer Research (AACR) Annual Meeting.

Transcript
Hi, my name is Joana Rodrigues. I'm a fourth year PhD student at the Department of Immunotechnology, Lund University, in Sweden.

Oncology Learning Network: What existing data led you and your co-investigators to conduct this research?

Dr Rodrigues: A previous study from our group focusing on MCL showed that CD163-positive macrophages were associated with worse outcomes in both a population-based cohort and the clinical trial cohort.

Further studies have also been shown previously that there is a key role in microphages as being a tool for the development and progression of MCL.

OLN: Could you briefly describe the study and its findings?

Dr Rodrigues: As we were trying to understand exactly how this communication and talk between the MCL cells and the microphages happen, we took advantage of a new technology, so the digital space profiling technology from NanoString. We have access to roughly 135 samples from different patients. We sampled those for CD163-positive microphages and then also tumor cells.

Our hypothesis is based on the fact that we think that microphages behave differently if they are in close proximity with tumor cells, and if they are a little bit further away. We tried to understand if they expressed different proteins that could be modulated to change how they respond to treatment.

Our main finding so far in this preliminary study has been that indeed they are different. They express different molecules.

An interesting one was that the microphages that were further away from the tumor cells, and they were actually in an area with a higher identity of T-cells, they express an immune checkpoint called VISTA, which is known to block T-cell activation.

OLN: Were any of the outcomes particularly surprising?

Dr Rodrigues: The surprising outcome for us was when we looked at the microphages that were very proximal to the tumor cells, we didn't really find an immune checkpoint activated in as opposites.

They were high in DNA repair molecules, so that was surprising. It was something that we were not really expecting.

OLN: What are the possible real-world applications of these findings in clinical practice?

Dr Rodrigues: Since we believe that microphages are a key component for the MCL development, and clearly, they're extremely associated with prognostic.

We think that by identifying these molecules, we'll be able to find a way to modulate them into new therapies for these patients.

OLN: Do you and your co-investigators indent to expand upon this research? If so, what will be your next steps?

Dr Rodrigues: At the moment, we're also looking at the tumor cells—so what changes when they are with microphages in close proximity, or even if don't have any. We also intend to look at the cells for the T-cell profile.

This first study was based on proteins, but we also apply it now where we are in the process of applying it now, to the transcriptomic profile also by NanoString.

We hope to combine both studies to get a little bit more of an overview of how this crosstalk happens. Then of course further on, we will need to evaluate our roles.

OLN: Is there anything else pertaining to your research and findings that you would like to add?

Dr Rodrigues: I just wanted to highlight the power of doing this research in tissue samples, because right now what we're seeing is that the tissue, the localization profile, it impacts the different immune cells.

It's an advantage and something that we're really focusing on into understanding, not only their profile, but how the spatial analysis looks like. This, we think it's a very strong advantage in the technology and in our study.

Source:
Rodrigues JM, Lokhande L, Gerdtsson AS, et al. Spatially resolved multiplexed analysis reveals how macrophages adapt to the mantle cell lymphoma microenvironment. Abstract presented at: AACR Annual Meeting; April 8-13, 2022; New Orleans, LA. Abstract 2026/4.