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| Item Type: | Article |
|---|---|
| Title: | LPL-positive endothelial cells control T-cell homing in liver metastasis |
| Creators: |
Zhang, Xiaowen  ORCID: https://orcid.org/0009-0006-3706-6849, Kamiyama, Miki ORCID: https://orcid.org/0000-0002-9817-6703, Tulessin, Margaret ORCID: https://orcid.org/0009-0009-3854-5288, Rinck, Lorna ORCID: https://orcid.org/0009-0004-4198-7654, Mallm, Jan-Philipp ORCID: https://orcid.org/0000-0002-7059-4030, Kilian, Michael ORCID: https://orcid.org/0000-0002-1946-3174, Agardy, Dennis A. ORCID: https://orcid.org/0000-0001-6900-2504, Heikenwälder, Mathias ORCID: https://orcid.org/0000-0002-3135-2274, Platten, Michael ORCID: https://orcid.org/0000-0002-4746-887X, Mogler, Carolin ORCID: https://orcid.org/0000-0003-3400-7254, Singhal, Mahak ORCID: https://orcid.org/0000-0002-7303-9585 and Augustin, Hellmut G. ORCID: https://orcid.org/0000-0002-7173-4242
|
| 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. SIGNIFICANCE: 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. |
| Source: | Cancer Discovery |
| ISSN: | 2159-8274 |
| Publisher: | American Association for Cancer Research |
| Page Range: | OF1-OF21 |
| Date: | 20 July 2026 |
| Official Publication: | https://doi.org/10.1158/2159-8290.cd-25-1411 |
| PubMed: | View item in PubMed |
| Related to: |
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