Method Profile

Native-Immune Lung ALI Organoids for Checkpoint and Radiation Comparisons

Compare lung-cancer culture formats and use a short native-immune window for pembrolizumab and radiation–STING testing.

LungOrganoids
Colorized scanning electron micrograph of a teal T lymphocyte.
Colorized scanning electron micrograph of a healthy T lymphocyte. (NIAID, CC BY 2.0)

Research Applications

Preclinical treatment comparison with retained endogenous immune cells and explicit passage limits.

Model & Design

Patient lung-cancer cell-based ALI organoids compared with minced-tissue ALI and conventional domes, with or without IL-2.

Experimental Format

Culture yield and immune retention characterization, day-15 single-cell profiling, seven-day pembrolizumab assay and radiation follow-up to day 24.

Model Components

  • Component

    Drug and radiation comparisons

    Description

    Pembrolizumab 10 μg/mL versus IgG4 for seven days. Radiation 0/4/8/16 Gy; four models tested diABZI 5 μM for two hours daily for four days after radiation, against monotherapies.

  • Component

    Readouts

    Description

    Organoid formation/area, immune fractions, single-cell composition, granzyme B/IFNγ and IFIT1/IFIT2/IFNB1 expression. Native immune abundance and culture state decline with passage.

Measurements & Endpoints

  • Organoid establishment and area
  • Immune retention and cell states
  • Checkpoint-associated viability and immune markers
  • Radiation–STING structural and expression response

Analysis

Evaluate formation in paired formats and use first-passage cultures for treatment comparisons. Keep immune composition, cytokine/granzyme changes and structural collapse as distinct outcomes.

Published Evidence

  • Study Sample

    16/19 cultures established; direct method comparison four patients, matched immune comparison three, pembrolizumab five and radiation–STING four. The single-cell donor count was not specified.

    Comparison

    Tissue ALI, domes ± IL-2, IgG4, radiation and diABZI monotherapies.

    Finding

    Cell-based ALI improved paired formation and immune retention. IL-2 did not significantly improve overall primary immune fractions and impaired subsequent organoid growth. Pembrolizumab responses occurred in two of five models; radiation plus diABZI caused greater collapse than either treatment alone.

    Interpretation & Limits
    • Native immune fractions decline and cultured cell states differ from source tissue.
    • No paired clinical checkpoint-response validation; a population-rate comparison does not validate individual prediction.
    • Small treatment subsets and area endpoints do not establish clinical radiation dose reduction.
    Study Design

    Primary study comparisons of the stated models, treatments and measurements.

Sources

  1. Optimized patient-derived lung cancer organoids recapitulating the immune landscape for precision therapy evaluation. Cellular Oncology (2026). ↗