TCR Repertoire Changes during TIL Expansion: Clonal Selection or Drifting?

Area of Science:

• Immunology
• Cancer Biology
• Cellular Therapy

Background:

• Tumor-infiltrating lymphocytes (TILs) are crucial for antitumor immunity.
• Ex vivo expansion of TILs is a promising cancer immunotherapy strategy.
• Monitoring the T-cell repertoire during expansion is essential for therapeutic efficacy.

Purpose of the Study:

• To investigate the utility of T-cell receptor beta (TCRβ) analysis for monitoring TIL clonotypic composition during IL2-mediated ex vivo expansion.
• To assess the impact of differential T-cell clone outgrowth on the antitumor reactivity of expanded TILs.

Main Methods:

• TCRβ sequencing to analyze the clonotypic repertoire of TILs.
• Ex vivo expansion of TILs in the presence of Interleukin-2 (IL2).
• Assessment of T-cell proliferation and antitumor activity.

Main Results:

• TCRβ analysis effectively monitored shifts in TIL clonotypic composition during IL2 expansion.
• Infrequent T-cell receptor beta clonotypes with higher proliferative potential often outcompeted dominant clones.
• This selective outgrowth potentially alters the overall antitumor reactivity of the expanded TIL product.

Conclusions:

• TCRβ repertoire analysis is a valuable tool for characterizing TIL expansion dynamics.
• The proliferative capacity of specific T-cell clones can significantly influence the composition of expanded TILs.
• Understanding and controlling TIL clonotypic changes are critical for optimizing adoptive T-cell immunotherapies.