Evidence map›Paper›PMID 42122216›Full record

ArticleCancers2026

Spatial Proximity Between PD-L1(+) Tumor-Associated Macrophages and CD8(+) T Cells Influences Response to Atezolizumab Plus Bevacizumab in Hepatocellular Carcinoma.

Takuto Nosaka, Masahiro Ohtani, Junki Yamashita, Yosuke Murata, Yu Akazawa, Tomoko Tanaka, Kazuto Takahashi, Tatsushi Naito, Yoshiaki Imamura, Kenji Koneri and 2 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cancers, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors.

Takuto NosakaSecond Department of Internal Medicine, Faculty of Medical Sciences, University of Fukui, Fukui 910-1193, Japan.ORCID 0000-0002-1929-7305
Masahiro OhtaniSecond Department of Internal Medicine, Faculty of Medical Sciences, University of Fukui, Fukui 910-1193, Japan.
Junki YamashitaSecond Department of Internal Medicine, Faculty of Medical Sciences, University of Fukui, Fukui 910-1193, Japan.
Yosuke MurataSecond Department of Internal Medicine, Faculty of Medical Sciences, University of Fukui, Fukui 910-1193, Japan.
Yu AkazawaSecond Department of Internal Medicine, Faculty of Medical Sciences, University of Fukui, Fukui 910-1193, Japan.ORCID 0000-0002-8030-7373
Tomoko TanakaSecond Department of Internal Medicine, Faculty of Medical Sciences, University of Fukui, Fukui 910-1193, Japan.ORCID 0000-0002-5768-3805
Kazuto TakahashiSecond Department of Internal Medicine, Faculty of Medical Sciences, University of Fukui, Fukui 910-1193, Japan.
Tatsushi NaitoSecond Department of Internal Medicine, Faculty of Medical Sciences, University of Fukui, Fukui 910-1193, Japan.ORCID 0000-0001-5472-8193
Yoshiaki ImamuraDivision of Diagnostic Pathology/Surgical Pathology, University of Fukui Hospital, Fukui 910-1193, Japan.ORCID 0000-0001-6439-0237
Kenji KoneriFirst Department of Surgery, Faculty of Medical Sciences, University of Fukui, Fukui 910-1193, Japan.
Takanori GoiFirst Department of Surgery, Faculty of Medical Sciences, University of Fukui, Fukui 910-1193, Japan.ORCID 0000-0001-7671-0648
Yasunari NakamotoSecond Department of Internal Medicine, Faculty of Medical Sciences, University of Fukui, Fukui 910-1193, Japan.ORCID 0000-0002-3160-3555

Funding

Japan Agency for Medical Research and Development JP26fk0210174Japan Agency for Medical Research and Development JP26fk0310529Japan Society for the Promotion of Science JP25K11170
6 · The paper itself

Abstract

backgroundResponses to atezolizumab plus bevacizumab (Atezo+Bev) in hepatocellular carcinoma (HCC) are heterogeneous, and response determinants remain unclear. We investigated whether spatial proximity between PD-L1(+) tumor-associated macrophages (TAMs) and CD8(+) T cells represents an immune niche associated with Atezo+Bev responsiveness.

methodsMultiplex immunohistochemistry was performed on biopsies from patients treated with Atezo+Bev (

resultsIn a patient with responsive and non-responsive lesions, the responsive lesion showed closer PD-L1(+) TAM-CD8(+) T cell proximity. In cohort analyses, the interaction variable was associated with tumor shrinkage and prolonged PFS in the Atezo+Bev group, whereas PD-L1(+) TAM or CD8(+) T cell density alone was not predictive. This association was absent in the lenvatinib cohort. High-interaction tumors showed increased GZMB(+) and TIM3(+) CD8(+) T cells. Transcriptomic analysis revealed the upregulation of inflammatory, cytotoxic, chemotactic, and immunoregulatory genes, with enrichment of the chemokine, IFN-gamma, and IL-10 signaling pathways.

conclusionsSpatial proximity between PD-L1(+) TAMs and CD8(+) T cells defines an immune niche characterized by coexisting immune activation and regulatory programs and is strongly associated with Atezo+Bev responsiveness in HCC. Quantification of this spatial interaction may serve as a biopsy-based biomarker for immunotherapy stratification.

Indexed as

atezolizumab plus bevacizumabCD8(+) T cellshepatocellular carcinomaspatial immune interactionstumor-associated macrophages

Identifiers

PMID42122216
PMCPMC13162669

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