Data · dataset · 2026

Spatiotemporal dynamics of the TME-immune ecosystem in solid tumors

Listed in ZivaHub and Deakin Research Online — shown once because both records carry DOI 10.69622/33349884

The tumor microenvironment (TME) is a complex, dynamic ecosystem where cancer cells, stromal cells, and immune cells interact within spatially defined niches, thereby shaping tumor progression, immune evasion, and therapeutic response.

Description

Despite advances in single-cell profiling, the spatiotemporal principles governing TME organization remain incompletely understood. This thesis integrates spatial multi-omics technologies with a novel computational pathology framework to systematically dissect the spatiotemporal dynamics of TME-immune ecosystems in solid tumors, using colorectal cancer (CRC) and hepatocellular carcinoma (HCC) as model systems.We developed a segmentation-free, pixel-based image analysis pipeline that enables high-throughput quantification of cellular spatial distributions, neighborhood relationships, and architectural organization from multiplexed tissue images.

Applying this framework across multiple independent cohorts, we made the following core discoveries.In Paper I, we systematically characterized perivascular niche cell heterogeneity in CRC and uncovered that these cells exhibit a compartmentalized, layered architecture around blood vessels. Specific vascular niche phenotypes were independently associated with poor prognosis. The segmentation-free pipeline developed here served as the methodological foundation for all subsequent spatial analyses.In Paper II, we identified recurrent tumor-associated macrophages (TAMs) dispersal phenotypes in CRC and demonstrated that specific spatial clustering patterns serve as independent prognostic factors.

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This revealed that the spatial sociology of macrophages carries prognostic information beyond simple density measurements.In Paper III, through a pan-cancer analysis of over 7,900 H&E images across 21 tumor types, we established that nearest neighbor distance (NND) serves as a spatial proxy for mechanical crowding. This metric was associated with Hippo/YAP/TAZ pathway activation and CD4+ memory T cell (CD4+ TMem cell) enrichment, defining a spatial-mechanical-immune axis with pan-cancer prognostic significance.In Paper IV, we discovered that in early-relapse HCC, tumor-infiltrating mature regulatory dendritic cells (mregDCs) establish a self-reinforcing immunosuppressive loop with CD161+CD8+ T cells via TNF-a/TNFR2/non-canonical NF-KB signaling and CCL20-CCR6 chemotaxis.

We demonstrated that TNFR2 blockade combined with anti-PD-L1 therapy achieves superior antitumor efficacy in mregDC-rich tumors.Collectively, this work establishes that the spatiotemporal organization of the TME-immune ecosystem is a critical biological dimension carrying clinically actionable information. Our findings provide mechanistic insights into TME dynamics during tumor recurrence and introduce a broadly applicable computational framework for spatial biomarker discovery in precision oncology.<h3 dir="ltr">List of scientific papers</h3>I. Huang L*, Herrera M, Sjölund J, Chocoloff V, Joost S, Tabiev RM, Wik Leiss L, Strell C, Nunes L, Mezheyeuski A, Edler D, Pontén F, Glimelius B, Sjöblom T, Kasper M, Pietras K, Östman A, Sun Y. A novel cell-segmentation-free image-analysis pipeline identifies complex colorectal cancer perivascular niches associated with outcome.

[Submitted]II. Huang L*, Sjöblom T, Glimelius B, Östman A, Sun Y. Computational imaging phenotyping of perivascular macrophages identifies dispersal patterns associated with prognosis in colorectal cancer. [Manuscript]III. Huang L*, Östman A, Sun Y. Pan-cancer atlas of cellular architecture reveals a nearest- neighbor distance-associated biomechanical-immune axis involving CD4+ memory T cells.

Clin Transl Med. 2026 Jul;16(7):e70742. <a href="doi.org/10.1002/ctm2.70742" target="_blank" rel="noreferrer">doi.org/10.1002/ctm2.70742</a>IV. Zhang Z†, Ding L†, Zhong Y†, Feng H†, Huang L†, Huang W, Wang C, Östman A, Wang B, Zhou J, Fan J, Guo W*, Wu L*, Sun Y*. Tumor-infiltrating mregDCs restrain anti-tumor immunity in early relapse HCC.

Adv Sci (Weinh). 2026 Aug;13(45):e75695. Epub 2026 May 14. <a href="doi.org/10.1002/advs.75695" target="_blank" rel="noreferrer">doi.org/10.1002/advs.75695</a>† Equal contribution (co-first authors). * Corresponding authors.

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From keywords: Earth & Environmental Science · Earth & Environmental Science
Inferred from text: Cancer 75% · Image 75% · Imaging 75%

Provenance · 2 source records, 10 field assertions

Source	Key	Last seen	Raw
ZivaHub	oai:figshare.com:article/33349884	12 d ago	JSON v1
Deakin Research Online	oai:figshare.com:article/33349884	12 d ago	JSON v1

Field	Assertion	Extractor	Evidence
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concepts[field].local:field:earth-environmental	mapping · dro deakin edu au	connector:dro_deakin_edu_au@1.0.0
concepts[modality].local:modality:image	enrichment · zivahub uct ac za	keyword-concept-rules@1.0.0	title+description (75%)
concepts[modality].local:modality:imaging	enrichment · zivahub uct ac za	keyword-concept-rules@1.0.0	title+description (75%)
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title	source · zivahub uct ac za	connector:zivahub_uct_ac_za@1.0.0	/metadata/dc/title

Spatiotemporal dynamics of the TME-immune ecosystem in solid tumors

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