Abstract P88: Hydrogel-Supported Cryopreserved Colorectal Cancer (CRC) Explants for Evaluation of Immunotherapy
Rockie Haiyao Ding, Kenny Zhuoran Wu, Tianyi Zhang, Johnny Chin-Ann Ong, Iain Bee Huat Tan, Eliza Li Shan FongBackground:
The heterogeneous tumor microenvironment (TME) in colorectal cancer (CRC) critically influences drug response, with Microsatellite Instability (MSI) and Microsatellite Stability (MSS) subtypes exhibiting distinct TMEs. While MSI tumors often respond to immunotherapy, MSS tumors are largely resistant. Current preclinical CRC models fail to fully recapitulate the immune landscape of these subtypes, limiting our understanding of how MSS tumors resist immunotherapy in vivo. To address this gap, we developed hydrogel-supported patient-derived tumor explant (PDTE) models that preserve the original TME of both MSI and MSS tumors. We further demonstrate use of these models for the assessment of pembrolizumab, an immune checkpoint inhibitor.
Methods:
21 resected CRC tumor fragments were cryopreserved in FBS/DMSO for up to 5 years. Upon thawing, sectioned 300-micron slices were cultured ex vivo in bioengineered hyaluronan (HA)-based hydrogels for ≥ 7 days. Tumor viability and histological composition were determined to evaluate PDTE outcome ex vivo. 8 MSI and 13 MSS PDTEs were treated with pembrolizumab and analyzed for immune response using multiplexed assays. Responders were predicted by correlating immune profiles with established prognostic markers (CXCL1, CXCL5, CXCL9, CXCL10), reported previously.
Results:
Hydrogel-supported tumor slices maintained viability and histological integrity for ≥ 7 days. Pembrolizumab treatment revealed subtype-specific immune responses. Notably, most MSI samples (6/8) identified as responders, while only 2/13 MSS samples responded—consistent with clinical observations.
Conclusions:
This study presents a robust ex vivo platform for preserving CRC TME, enabling accurate prediction of anti-PD1 clinical response. The model holds promise for preclinical immunotherapy assessment beyond PD-1 blockade and for elucidating the biology of MSS/MSI CRC.
Citation Format:
Rockie Haiyao Ding , Kenny Zhuoran Wu, Tianyi Zhang, Johnny Chin-Ann Ong, Iain Bee Huat, Eliza Li Shan. Hydrogel-Supported Cryopreserved Colorectal Cancer (CRC) Explants for Evaluation of Immunotherapy [abstract]. In: Proceedings of Frontiers in Cancer Science 2025; 2025 Nov 5-7; Singapore. Philadelphia (PA): AACR; Cancer Res 2026;86(13_Suppl):Abstract nr P88.