Year: 2026
Type: preprint
Study design: Observational Study
Abstract: Immunotherapy has transformed treatment for many cancers. In the aggressive and genetically heterogeneous diffuse large B-cell lymphoma (DLBCL), CD19 CAR T-cell therapy is highly effective, whereas immune checkpoint blockade has shown limited benefit. Loss of MHC expression is a common mechanism to escape T-cell cytotoxicity, and loss of MHC class I (MHC-I) and II are frequent in DLBCL. We applied imaging mass cytometry to diagnostic biopsies from younger, high-risk DLBCL patients to map the tumor microenvironment (TME) spatial architecture in relation to tumor cell MHC expression, mutational status, transcriptomic and proteomic profiles. Neighborhood analyses identified four TME subtypes: immune-cell depleted and three immune-infiltrated types (mixed, CD4 T cell-rich, CD8 T-cell/macrophage-rich). Depleted cases had shorter overall survival ( p = 0.033) and increased expression of proteins involved in DNA replication and proliferation markers compared to infiltrated cases. Tumor cell MHC-I expression was heterogeneous. Cases with low frequency of MHC-I pos tumor cells were enriched for the depleted TME type. MHC-I pos tumor cells were surrounded by CD4 and CD8 T cells and M1 macrophages, whereas MHC-I neg tumor cells were closer to other MHC-I neg tumor cells. These findings suggest that TME-based classification incorporating tumor cell MHC-I status may improve individualized immunotherapy selection.
Authors: Kanutte Huse, Yngvild N. Blaker, Jillian F. Wise, Marie Hairing Enemark, Maare Arffman, Ankush Sharma, Leo Meriranta, Sigve Nakken, Kathrine Isaksen, Ivana Spasevska, Vera Hilden, Chloé B. Steen, David Warren, Bent Honoré, Klaus Beiske, Erlend B. Smeland, Qiang Pan-Hammarström, Maja Ludvigsen, Sirpa Leppä, Harald Holte, June H. Myklebust
Language: English
Subfield: Pathology and Forensic Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W7207655316