Journal Article

DKFZ-2025-01589

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Spatial tumor immune microenvironment as a prognostic and predictive biomarker in anti-EGFR-based maintenance for RAS wt metastatic CRC - the PanaMa (AIO KRK0212) trial.

Ballhausen, A. ; Swoboda, S. ; Horst, D. ; Fruehauf, S. ; Graeven, U. ; Müller, L. ; Trarbach, T. ; Fischer von Weikersthal, L. ; Goekkurt, E. ; Heinemann, V. ; Kasper, S.Extern* ; Kurreck, A. ; Alig, A. H. S. ; Reinacher-Schick, A. C. ; Bullinger, L.DKFZ* ; Stahler, A. ; Stintzing, S.DKFZ* ; Jarosch, A. ; Modest, D. P.DKFZ*

2025
AACR Philadelphia, Pa. [u.a.]

Abstract: Tumor immune cell infiltration patterns in the tumor microenvironment serve as prognostic biomarkers in metastatic colorectal cancer (mCRC). This study analyzed the spatially resolved tumor immune microenvironment for prognostic and predictive impact in patients with RAS wildtype mCRC receiving FU/FA ± Pmab maintenance after Pmab + FOLFOX induction (PanaMa AIO KRK0212; NCT01991873).Twelve immune parameters (lymphocyte markers: CD3, CD8, CD45RO, FOXP3, CD20, Granzyme B, Perforin; immune checkpoints: PD-1, PD-L1, IDO1, LAG3; monocyte marker CD163) were quantified in spatially resolved tumor and stroma regions (invasive-margin [Inv], center [Cen]) on tissue microarrays from available surgical resections using digital pathology. Prognostic and predictive associations were assessed using percentile cutoffs, immunoscore (IS), PD-L1 CPS, and an immunoactivation score (IAS). Median progression-free (PFS) and overall survival (OS) were estimated by Kaplan-Meier-method, log rank test and Cox regression.In 194 patients, low CD163 and high PD-1 in the tumor center were independent prognostic factors for prolonged PFS, while high central LAG3 was associated with improved OS. Pmab maintenance conferred PFS benefit in patients with low CD3InvStr, CD8Inv, LAG3CenTum, CD163CenTum, IS, and high CD45ROCen. CD45ROCen-high and LAG3Cen-low also predicted OS benefit. A positive IAS (≥2 predictive markers) identified patients deriving significant PFS (HR 0.50, 95% CI 0.32-0.76; P<0.001) and OS (HR 0.54, 95% CI 0.33-0.86; P=0.009) benefit from Pmab.Immune microenvironment factors, including CD3, CD8, CD163, LAG3, CD45RO, IS, and IAS, predict benefit from Pmab maintenance, suggesting immune activation as a key component of anti-EGFR efficacy.

Note: 2025 Oct 1;31(19):4049-4058

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Contributing Institute(s):

1. DKTK Koordinierungsstelle München (MU01)
2. DKTK Koordinierungsstelle Berlin (BE01)

Research Program(s):

1. 899 - ohne Topic (POF4-899) (POF4-899)

Appears in the scientific report 2025

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Database coverage:
; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; Essential Science Indicators ; IF >= 10 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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