Terkild Brink Buus

@terkild.bsky.social

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Associate Professor intrigued by skin immunology, T cell lymphoma, S. aureus-T cell interactions and single-cell analyses at University of Copenhagen @ucph.bsky.social @sic-ucph.bsky.social

Mouse skin sections from the EL4 lymphoma model comparing vehicle-treated and antibiotic-treated animals, stained for filaggrin in non-lesional and tumour-adjacent epidermis. Vehicle-treated mice show reduced filaggrin near tumour regions, whereas antibiotic-treated mice retain stronger, more near-normal epidermal staining. This matters because it provides in vivo support that bacterial control can preserve barrier integrity in lymphoma-associated skin disease.
Immunohistochemistry from a CTCL patient comparing non-lesional skin, lesional skin before antibiotics, and lesional skin after antibiotics, stained for filaggrin, filaggrin-2, and loricrin. Barrier-protein staining is reduced in the lesion at baseline and increases after antibiotic treatment. This is important because it links bacterial eradication to partial restoration of epidermal barrier markers in patient skin.
Single-cell and cytokine-expression panels showing that staphylococcal enterotoxin stimulation induces inflammatory cytokines in CTCL samples, with contributions from both malignant and non-malignant cell populations. Cytokines highlighted include OSM, IL-13, IL-22, TNF, IFNG, IL-6, and IL-17. This matters because it identifies the cellular sources of the barrier-repressing inflammatory program and shows that both tumor and non-tumor immune compartments participate.
Bar plots showing keratinocyte expression of FLG, FLG2, LOR, and KRT14 after exposure to supernatants from SE-stimulated CTCL cells, with or without JAK inhibition. SE-conditioned supernatants suppress FLG, FLG2, and LOR, while JAK inhibition largely restores their expression; KRT14 changes little. This is important because it argues that barrier repression is selective and largely mediated through cytokine-driven JAK/STAT signaling rather than nonspecific toxicity.
Schematic of the experimental design. S. aureus supernatant or a purified staphylococcal enterotoxin pool is added to CTCL patient cells, supernatants from these cultures are then transferred to keratinocytes, and barrier-gene expression is measured. This panel is important because it defines the causal chain tested in the study: bacterial products activate CTCL-associated T cells, which then alter keratinocyte barrier programs.
Front page of article Buus et al. 2025 Cancer Discovery, including graphics showing red and orange malignant T cell subclones in a blue skin environment.
Schematic figure showing divergent evolution of malignant subclones and how they migrate to different tissue compartments (blood vs skin), respond differently to extrinsic stimuli such as Staphylococcus aureus enterotoxins, and how subclones differ in their intrinsic resistance to anti-cancer drugs.
Figure showing marked difference in the degree a clinically relevant anti-cancer drug (HDAC-inhibitor) induced cell death between divergent malignant subclones from a L-CTCL patient. Similar analyses across 6 different anti-cancer drugs (Vorinostat, Romidepsin, Etoposide, Oligomycin, Doxorubicin and Bortezomib) is summarize for subclones across 12 L-CTCL patients by flow cytometry. Also shows schematic conclusion figure showin that the subclones that are most responsive to extrinsic stimuli such as Staphylococcus aureus enterotoxins (SE) are also the most sensitive to anti-cancer drugs - but only if the stimuli are removed. Other subclones that do not respond to extrinsic stimuli are intrinsically more drug-resistant.
Figure showing differential activation of two malignant subclone from a L-CTCL patient following exposure to Staphylococcus aureus supernatants. Similar analysis across subclones from 16 L-CTCL patients is shown which highlights that divergent subclones can be divided into four distinct Staphylococcus aureus enterotoxin (SE) response groups and that the subclones assigned to group 3 all exhibit higher levels of proliferation than their neighboring subclones when cultured in the presence of SE. Final schematic is summarizing this by showing that divergent subclones respond differential to enterotoxins leading to increased activation, transcription and proliferation of responsive subclones.
Plots and schematic showing experimental setup for matched blood and skin (separated into dermis and epidermis for further spatial detail). Barplots showing subclone abundance across three patients across blood, dermis and epidermis from two independent lesional sites. Also includes a schematic figure showing that malignant subclones exhibit differences in the tissue preference - some prefer blood, others prefer dermis or epidermis. Final plot shows correlation between subclones’ ability to respond to their (inflammatory) environment and their proliferation (indicating aggressiveness) in the skin. Schematic showing that the subclone most abundant in blood (shown in red) tends to have lower levels of interaction with the microenvironment in the skin - leading to a growth advantage of the responsive subclones.
Schematic figure showing experimental setup with collection of matched blood and skin samples from 57 leukemic cutaneous T-cell lymphoma (L-CTCL) patients as well as the multimodal single-cell analysis approach combining single-cell T-cell receptor (scTCR) and cellular indexing of transcriptomes and epitopes (CITE) sequencing: scTCR+CITE-seq. Also showing data from each of the 57 included L-CTCL patients showing their relative abundance of different subclones as percentage of total CD4+ T cell population. This plot shows that distinct malignant subclones could be identified in more than 80% of the L-CTCL patients. Final plot shows that subclones co-exist over extended periods of time by a connected barplot with subclone abundance at multiple timepoints up to 294 days.
Schematic figure showing experimental setup with collection of matched blood and skin samples from 57 leukemic cutaneous T-cell lymphoma (L-CTCL) patients as well as the multimodal single-cell analysis approach combining single-cell T-cell receptor (scTCR) and cellular indexing of transcriptomes and epitopes (CITE) sequencing: scTCR+CITE-seq. Figure shows the five main findings of the study: 1. Divergent evolution resulting in multiple subclones with distinct extrinsic responsiveness and intrinsic drug resistance, 2. Subclones are functionally and genomically distinct, 3. Subclones home to different tissue niches (some prefer blood whereas others prefer the dermis or epidermis of the skin), 4. Divergent subclones exhibit differences in their induced aggressiveness visualized by different response to Staphylococcus aureus enterotoxins, and 5. Divergent subclones exhibit differences in their intrinsic drug resistance. Aggressive subclones become sensitive to treatment when their extrinsic stimuli are removed.
Schematic figure showing divergent evolution of malignant subclones and how they migrate to different tissue compartments (blood vs skin), respond differently to extrinsic stimuli such as Staphylococcus aureus enterotoxins, and how subclones differ in their intrinsic resistance to anti-cancer drugs.
Schematic figure showing divergent evolution of malignant subclones and how they migrate to different tissue compartments (blood vs skin), respond differently to extrinsic stimuli such as Staphylococcus aureus enterotoxins, and how subclones differ in their intrinsic resistance to anti-cancer drugs.
Figure showing marked difference in the degree a clinically relevant anti-cancer drug (HDAC-inhibitor) induced cell death between divergent malignant subclones from a L-CTCL patient. Similar analyses across 6 different anti-cancer drugs (Vorinostat, Romidepsin, Etoposide, Oligomycin, Doxorubicin and Bortezomib) is summarize for subclones across 12 L-CTCL patients by flow cytometry. Also shows schematic conclusion figure showin that the subclones that are most responsive to extrinsic stimuli such as Staphylococcus aureus enterotoxins (SE) are also the most sensitive to anti-cancer drugs - but only if the stimuli are removed. Other subclones that do not respond to extrinsic stimuli are intrinsically more drug-resistant.
Figure showing differential activation of two malignant subclone from a L-CTCL patient following exposure to Staphylococcus aureus supernatants. Similar analysis across subclones from 16 L-CTCL patients is shown which highlights that divergent subclones can be divided into four distinct Staphylococcus aureus enterotoxin (SE) response groups and that the subclones assigned to group 3 all exhibit higher levels of proliferation than their neighboring subclones when cultured in the presence of SE. Final schematic is summarizing this by showing that divergent subclones respond differential to enterotoxins leading to increased activation, transcription and proliferation of responsive subclones.
Plots and schematic showing experimental setup for matched blood and skin (separated into dermis and epidermis for further spatial detail). Barplots showing subclone abundance across three patients across blood, dermis and epidermis from two independent lesional sites. Also includes a schematic figure showing that malignant subclones exhibit differences in the tissue preference - some prefer blood, others prefer dermis or epidermis. Final plot shows correlation between subclones’ ability to respond to their (inflammatory) environment and their proliferation (indicating aggressiveness) in the skin. Schematic showing that the subclone most abundant in blood (shown in red) tends to have lower levels of interaction with the microenvironment in the skin - leading to a growth advantage of the responsive subclones.
Schematic figure showing experimental setup with collection of matched blood and skin samples from 57 leukemic cutaneous T-cell lymphoma (L-CTCL) patients as well as the multimodal single-cell analysis approach combining single-cell T-cell receptor (scTCR) and cellular indexing of transcriptomes and epitopes (CITE) sequencing: scTCR+CITE-seq. Also showing data from each of the 57 included L-CTCL patients showing their relative abundance of different subclones as percentage of total CD4+ T cell population. This plot shows that distinct malignant subclones could be identified in more than 80% of the L-CTCL patients. Final plot shows that subclones co-exist over extended periods of time by a connected barplot with subclone abundance at multiple timepoints up to 294 days.
Schematic figure showing experimental setup with collection of matched blood and skin samples from 57 leukemic cutaneous T-cell lymphoma (L-CTCL) patients as well as the multimodal single-cell analysis approach combining single-cell T-cell receptor (scTCR) and cellular indexing of transcriptomes and epitopes (CITE) sequencing: scTCR+CITE-seq. Figure shows the five main findings of the study: 1. Divergent evolution resulting in multiple subclones with distinct extrinsic responsiveness and intrinsic drug resistance, 2. Subclones are functionally and genomically distinct, 3. Subclones home to different tissue niches (some prefer blood whereas others prefer the dermis or epidermis of the skin), 4. Divergent subclones exhibit differences in their induced aggressiveness visualized by different response to Staphylococcus aureus enterotoxins, and 5. Divergent subclones exhibit differences in their intrinsic drug resistance. Aggressive subclones become sensitive to treatment when their extrinsic stimuli are removed.