MC38 colorectal tumor cell lines from two different sources display substantial differences in transcriptome,...

Area of Science:

• Oncology
• Immunology
• Genomics

Background:

• The MC38 cell line is a widely used murine model for colorectal carcinoma, known for its high mutational burden and sensitivity to immunotherapy.
• Endogenous CD8+ T cell responses against neoantigens have been reported in this model.

Purpose of the Study:

• To compare the genomic and transcriptomic profiles of two distinct MC38 cell line sources (MC38-K and MC38-L).
• To analyze the differential recognition of these cell lines by CD8+ T cells based on neo-epitope specificity.

Main Methods:

• Whole exome and transcriptome re-sequencing of MC38-K and MC38-L cell lines.
• Genomic and transcriptomic data analysis, including variant calling and expression profiling.
• Assessment of CD8+ T cell recognition of neoantigens present in the cell lines.

Main Results:

• MC38-K and MC38-L cell lines display distinct genomic structures, ploidies, and mutational landscapes, with MC38-L having more variations.
• Mutational signatures and shared variants/fusion events differed significantly between the two cell lines.
• Previously identified neoantigens (e.g., Rpl18^mut, Adpgk^mut) were absent in MC38-K, leading to differential CD8+ T cell recognition and killing capacity.

Conclusions:

• At least two distinct sub-cell lines of MC38 exist, necessitating meticulous tracking for reproducible research.
• Understanding these genetic differences is crucial for accurate interpretation of immunological data and experimental outcomes.
• This study provides a reference for researchers selecting appropriate MC38 sub-cell lines for their studies.