Tumour budding and CD8+ T-cells: "attackers" and "defenders" in rectal cancer with and without neoadjuvant chemoradiotherapy.

Georges, Nadine DF; Oberli, Beatrice; Rau, Tilman; Galván, José; Nagtegaal, Iris D; Dawson, Heather; Blank, Annika; Kohler, Andreas; Lugli, Alessandro; Zlobec, Inti (2021). Tumour budding and CD8+ T-cells: "attackers" and "defenders" in rectal cancer with and without neoadjuvant chemoradiotherapy. Histopathology, 78(7), pp. 1009-1018. Wiley 10.1111/his.14319

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AIM

Tumour budding ("attacker") and CD8+ T-cells ("defender") are recognized as important parameters for risk stratification in colon cancers and combined, may have even stronger clinical impact. Here, we determine the value of tumor budding and CD8+ in rectal cancer patients treated with/without neoadjuvant therapy.

METHODS

Using digital scans of all tumor slides/case, we analysed CD8+ T-cell counts in two patient cohorts: 45 neoadjuvantly-treated and 47 primarily surgically-treated (totaling n=540 slides) after double-staining of the surgical resection specimen for pan-cytokeratin and CD8+. Tumour buds in hotspots were manually counted (area 0.785 mm2 ), CD8+ T-cell counts were analysed both in tumor budding hotspots and densest CD8+ regions throughout the tumor, separately.

RESULTS

In neoadjuvantly treated patients, only tumor budding and not CD8+ T-cells was associated with tumor features, including more advanced ypT (p=0.0062), venous invasion (p=0.002), lymphatic invasion (p=0.0003) and perineural invasion (p=0.0017) as well as higher AJCC tumor regression score (p=0.0035), indicating less tumor response. Overall survival was also worse in patients with high-grade budding in univariate analysis only. In contrast, all three variables, namely tumor budding (p=0.0347), CD8+ T-cells in budding hotspots (p=0.0382) and CD8+ T-cells in densest areas (p=0.0117) were associated with worse (budding) and better (CD8) survival time also in multivariate setting CONCLUSION: In rectal cancer, tumor budding has clinical relevance in both primarily surgically treated patients and in those with neoadjuvantly treated patients, where it characterizes highly aggressive residual disease. CD8+ T-cell counts appear not to have prognostic relevance in the neoadjuvant context.

Item Type:	Journal Article (Original Article)
Division/Institute:	04 Faculty of Medicine > Service Sector > Institute of Pathology 04 Faculty of Medicine > Service Sector > Institute of Pathology > Translational Research Unit 04 Faculty of Medicine > Service Sector > Institute of Pathology > Clinical Pathology 04 Faculty of Medicine > Department of Gastro-intestinal, Liver and Lung Disorders (DMLL) > Clinic of Visceral Surgery and Medicine > Visceral Surgery
UniBE Contributor:	Georges, Nadine Denise Françoise, Rau, Tilman, Galván Hernández, José Alberto, Dawson, Heather, Blank, Annika, Kohler, Andreas, Lugli, Alessandro, Zlobec, Inti
Subjects:	500 Science > 570 Life sciences; biology 600 Technology > 610 Medicine & health
ISSN:	1365-2559
Publisher:	Wiley
Language:	English
Submitter:	Inti Zlobec
Date Deposited:	01 Feb 2021 13:57
Last Modified:	05 Dec 2022 15:43
Publisher DOI:	10.1111/his.14319
PubMed ID:	33340423
Uncontrolled Keywords:	CD8 Rectal cancer digital image analysis neoadjuvant therapy tumour budding
URI:	https://boris.unibe.ch/id/eprint/150070