PUBLICATION
CRATER tumor niches facilitate CD8+ T cell engagement and correspond with immunotherapy success
- Authors
- Ludin, A., Stirtz, G.L., Tal, A., Nirmal, A.J., Pfaff, K.L., Manos, M., Besson, N., Eskndir, N., Porter, B., Jones, S.M., Faulkner, H.M., Gong, Q., Liu, S., Barrera, I., Wu, L., Pessoa Rodrigues, C., Sahu, A., Jerison, E., Alessi, J.V., Ricciuti, B., Richardson, D.S., Weiss, J.D., Moreau, H.M., Stanhope, M.E., Afeyan, A.B., Sefton, J., McCall, W.D., Formato, E., Yang, S., Zhou, Y., Hoytema van Konijnenburg, D.P., Cole, H.L., Cordova, M., Deng, L., Rajadhyaksha, M., Quake, S.R., Awad, M.M., Chen, F., Wucherpfennig, K.W., Sorger, P.K., Hodi, F.S., Rodig, S.J., Murphy, G.F., Zon, L.I.
- ID
- ZDB-PUB-251020-29
- Date
- 2025
- Source
- Cell : (Journal)
- Registered Authors
- Pfaff, Kathleen, Zhou, Yi, Zon, Leonard I.
- Keywords
- CD8+ T cells, cancer, immune response, immunotherapy, melanoma, zebrafish
- Datasets
- GEO:GSE213263, GEO:GSE213285, GEO:GSE312604, GEO:GSE213286
- MeSH Terms
-
- Animals
- Antigen Presentation
- CD8-Positive T-Lymphocytes*/immunology
- Cell Line, Tumor
- Humans
- Immune Checkpoint Inhibitors/therapeutic use
- Immunotherapy*/methods
- Melanoma*/immunology
- Melanoma*/pathology
- Melanoma*/therapy
- Tumor Microenvironment*/immunology
- Zebrafish
- PubMed
- 41109214 Full text @ Cell
Citation
Ludin, A., Stirtz, G.L., Tal, A., Nirmal, A.J., Pfaff, K.L., Manos, M., Besson, N., Eskndir, N., Porter, B., Jones, S.M., Faulkner, H.M., Gong, Q., Liu, S., Barrera, I., Wu, L., Pessoa Rodrigues, C., Sahu, A., Jerison, E., Alessi, J.V., Ricciuti, B., Richardson, D.S., Weiss, J.D., Moreau, H.M., Stanhope, M.E., Afeyan, A.B., Sefton, J., McCall, W.D., Formato, E., Yang, S., Zhou, Y., Hoytema van Konijnenburg, D.P., Cole, H.L., Cordova, M., Deng, L., Rajadhyaksha, M., Quake, S.R., Awad, M.M., Chen, F., Wucherpfennig, K.W., Sorger, P.K., Hodi, F.S., Rodig, S.J., Murphy, G.F., Zon, L.I. (2025) CRATER tumor niches facilitate CD8+ T cell engagement and correspond with immunotherapy success. Cell. :.
Abstract
T cell-mediated tumor killing underlies immunotherapy success. Here, we used long-term in vivo imaging and high-resolution spatial transcriptomics of zebrafish endogenous melanoma, as well as multiplex imaging of human melanoma, to identify domains facilitating the immune response during immunotherapy. We identified cancer regions of antigen presentation and T cell engagement and retention (CRATERs) as pockets at the stroma-melanocyte boundaries of zebrafish and human melanoma. CRATERs are rich in antigen-recognition molecules, harboring the highest density of CD8+ T cells in tumors. In zebrafish, CD8+ T cells formed prolonged interactions with melanoma cells within CRATERs, characteristic of antigen recognition. Following immunostimulatory treatment, CRATERs expanded, becoming the major sites of activated CD8+ T cell accumulation and tumor killing. In humans, elevation in CRATER density in biopsies following immune checkpoint blockade (ICB) therapy correlated with a clinical response to therapy. CRATERs are structures that show active tumor killing and may be useful as a diagnostic indicator for immunotherapy success.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping