What question did this study set out to answer?

To explore how different SARS-CoV-2 variants affect patient-derived tumor organoids across various cancer types.

January 25, 2026Open Access

Modulation of Patient-Derived Tumor Organoids by SARS-CoV-2 Variants Across Cancer Types: A Study Combining Morphology, Inflammation, and Whole-Exome Profiling

Key Points

To explore how different SARS-CoV-2 variants affect patient-derived tumor organoids across various cancer types.
Quantification of viral infection using RT-qPCR 24 hours post-infection.
Assessment of morphological changes in organoids post-infection.
Immune profiling of infection response in tumor organoids.
Whole-exome sequencing to identify host gene alterations.
Delta variant showed higher viral loads in lung and breast organoids.
Colorectal organoids had varying susceptibility to infections.
Infection caused reduced area and perimeter, and increased circularity of organoids.
Gamma variant lowered Interferon alpha levels in lung organoids and increased E-selectin in colorectal organoids.
Delta variant reduced multiple inflammatory markers in lung and breast organoids, while increasing MIP-1β in colorectal organoids.

Abstract

Cancer patients are highly vulnerable to severe COVID-19, requiring models that capture tumor–virus interactions. We investigated tumor- and variant-specific effects of SARS-CoV-2 Gamma and Delta infections using patient-derived organoids (PDOs) from metastatic breast, lung, and colorectal cancers. Viral infection was quantified by Real-Time Quantitative Polymerase Chain Reaction (RT-qPCR) 24 h post-infection, and morphological changes and immune mediators were profiled. Genomic analysis using whole-exome sequencing was performed to identify contributing host-related gene alterations. The Delta variant produced consistently higher viral loads in lung and breast PDOs, while colorectal PDOs showed variable susceptibility. Infection led to reduced area and perimeter and increased circularity across all tumor types. Immune profiling revealed distinct responses: Gamma decreased Interferon alpha (IFNα) in lung PDOs and increased E-selectin in colorectal PDOs. Delta broadly reduced inflammatory mediators in lung 10 kDa interferon gamma-induced protein (IP-10) and Intercellular adhesion molecule 1 (ICAM-1) and breast Interleukin-6 (IL-6), Interleukin-13 (IL-13), and Interleukin-17A (IL-17A) PDOs, while increasing Macrophage inflammatory protein 1-beta (MIP-1β) in colorectal PDOs. Host gene variants involved in trafficking (FYCO1 and RAB7A) and immune signaling (FOXA2, SFTPD, STAT3, and TET2) were associated with differential infection profiles. These findings show that SARS-CoV-2 induces variant- and tumor-specific morphological and immunological changes in cancer PDOs, highlighting the potential of this model to unravel host–virus interactions and identify genetic factors that shape infection outcomes in cancer.

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