Journal Article

DKFZ-2026-01815

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png LPL-Positive Endothelial Cells Control T-cell Homing in Liver Metastasis.

Zhang, X. (First author)DKFZ* ; Kamiyama, M. ; Tulessin, M. ; Rinck, L. ; Mallm, J.-P.DKFZ* ; Kilian, M.DKFZ* ; Agardy, D. A.DKFZ* ; Heikenwälder, M.DKFZ* ; Platten, M.DKFZ* ; Mogler, C. ; Singhal, M. ; Augustin, H. (Last author)DKFZ*

2026
[Verlag nicht ermittelbar] Philadelphia, Pa.

Abstract: Combination therapies involving vascular targeting drugs have shown promise in overcoming resistance to immunotherapy. However, the prerequisite for vascular modulation to evoke an effective antitumor T-cell response remains elusive. Tracing the transcriptional response of liver metastasis-associated peritumoral and tumor endothelial cells (TEC) to T-cell intervention, we discovered an immunomodulatory TEC subpopulation that highly expressed lipoprotein lipase (LPL). LPL+ TECs facilitated intratumoral homing of activated antitumor CD8+ T cells driving liver metastatic regression. Mechanistically, LPL enhanced MHC-I-dependent cross-presentation of tumor antigens on TECs for T-cell trafficking. Consequently, LPL+ TECs were recognized and targeted by T cells, further aiding antitumor response. Corresponding analyses of human liver metastasis samples identified a significant correlation between the presence of intratumoral LPL+ blood vessels and the accumulation of T cells. Altogether, the study identifies a decisive role of TECs in orchestrating an effective T-cell response by overcoming tumor's intrinsic insufficient antigen presentation.The study identifies LPL+ TECs as orchestrators of activated CD8+ T-cell homing into immunologically cold tumors with low baseline MHC-I expression. Enhancing tumor antigen exposure by MHC-I cross-presentation in TECs presents a promising approach to compensate the intrinsic inability of tumor cells and boost antitumor immunotherapy.

Note: #EA:A190#LA:A190# / #DKTKZFB26# / epub

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Contributing Institute(s):

1. Vaskuläre Onkologie und Metastasierung (A190)
2. Single-cell Open Lab (W192)
3. KKE Neuroimmunologie und Hirntumorimmunologie (D170)
4. Chronische Entzündung und Krebs (D440)
5. DKTK HD zentral (HD01)

Research Program(s):

1. 311 - Zellbiologie und Tumorbiologie (POF4-311) (POF4-311)

Appears in the scientific report 2026

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Database coverage:
; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Essential Science Indicators ; IF >= 25 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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