Immunotherapy in Soft Tissue Sarcomas-An Ongoing Quest

Area of Science:

• Oncology
• Immunology
• Cancer Research

Background:

• Soft tissue sarcomas (STSs) are rare, heterogeneous cancers with limited immunotherapy efficacy.
• Understanding biomarkers for immunotherapy response is crucial for improving treatment outcomes.

Purpose of the Study:

• To review biomarkers of immunotherapy sensitivity in STSs.
• To explore tumor-intrinsic features and tumor microenvironment (TME) signatures.
• To discuss strategies for enhancing STS immunogenicity.

Main Methods:

• Literature review focusing on STSs and immunotherapy biomarkers.
• Analysis of tumor-intrinsic factors (mutational burden, antigen expression).
• Evaluation of TME composition (tertiary lymphoid structures, immune cells) and its impact on response.

Main Results:

• Many STSs exhibit immune resistance due to low tumor mutational burden and suppressed antigen presentation.
• TME composition significantly influences immunotherapy response, with B-cell-rich tertiary lymphoid structures correlating with better outcomes.
• Adaptive immune responses within the TME are key determinants of sensitivity.

Conclusions:

• A shift towards a TME-inclusive strategy is needed for effective STS immunotherapy.
• Personalized immunotherapeutic strategies require consideration of both tumor and TME characteristics.
• Emerging strategies focus on enhancing tumor immunogenicity and remodeling the TME.