Isaksen, K. | bioRxiv Science

bioRxiv2026

Immune-cell depleted diffuse large B-cell lymphomas have reduced expression of MHC class I

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.

cancer biology↗

bioRxiv2021

Towards rainy Arctic winters: experimental icing impacts tundra plant productivity and reproduction

The Arctic is warming rapidly, with winters warming up to seven times as fast as summers in some regions. Warm spells in winter lead to more frequent extreme rain-on-snow events that alter snowpack conditions and can encapsulate tundra vegetation in basal ice ( icing) for several months. However, tundra climate change studies have mainly focused on summer warming. Here, we investigate icing effects on vascular plant phenology, productivity, and reproduction in a pioneer field experiment in high Arctic Svalbard, simulating rain-on-snow and resultant icing in five consecutive winters, assessing vascular plant responses throughout each subsequent growing season. We also tested whether icing responses were modified by experimentally increased summer temperatures. Icing alone delayed early phenology of the dominant shrub, Salix polaris, but with evidence for a catch-up (through shortened developmental phases and increased community-level primary production) later in the growing season. This compensatory response occurred at the expense of delayed seed maturation and reduced community-level inflorescence production. Both the phenological delay and allocation trade-offs were associated with icing-induced lags in spring thawing and warming of the soil, crucial to regulating plant nutrient availability and acquisition. Experimental summer warming modified icing effects by advancing and accelerating plant phenology (leaf and seed development), thus increasing primary productivity already early in the growing season, and partially offsetting negative icing effects on reproduction. Thus, winter and summer warming must be considered simultaneously to predict tundra plant climate change responses. Our findings demonstrate that winter warm spells can shape high Arctic plant communities to a similar level as summer warming. However, the absence of accumulated effects over the years reveals an overall resistant community which contrasts with earlier studies documenting major die-off. As rain-on-snow events will be rule rather than exception in most Arctic regions, we call for similar experiments in coordinated circumpolar monitoring programmes across tundra plant communities.

plant biology↗