Distinct T cell functions enable efficient immunoediting and prevent tumor emergence of developing sarcomas

Area of Science:

• Immunology
• Cancer Biology
• Tumor Microenvironment

Background:

• T cells are crucial for eliminating tumor cells expressing neoantigens.
• The precise mechanisms and timing of T cell-mediated tumor editing remain unclear.

Purpose of the Study:

• To investigate how T cells edit sarcomas by eliminating neoantigen-expressing cells.
• To determine the timing and mechanisms of T cell-mediated tumor suppression.

Main Methods:

• Utilized a murine sarcoma model with fluorescent neoantigens.
• Employed single-cell analyses to examine tumor cell populations and T cell infiltration.
• Investigated the roles of IFNγ and PD-L1 in T cell-mediated tumor editing.

Main Results:

• Tumor development was significantly reduced in T cell-sufficient mice compared to T cell-deficient mice.
• Emergent tumor cells in T cell-sufficient mice had silenced neoantigens, but neoantigen-negative cells were also present.
• T cell infiltration and elimination of tumor cells occurred within 8 days, particularly when neoantigen loss was manipulated early.
• T cell-dependent upregulation of PD-L1 and IFNγ-response genes was observed.
• T cell depletion rescued both neoantigen-positive and -negative cells, while IFNγ blockade only rescued negative cells.

Conclusions:

• T cells effectively edit sarcomas by eliminating neoantigen-expressing cells.
• T cells prevent early tumor formation through both IFNγ-independent and IFNγ-dependent (bystander) mechanisms.