Exomics and immunogenics: Bridging mutational load and immune checkpoints efficacy

Area of Science:

• Oncology
• Immunotherapy
• Cancer Genomics

Background:

• Anti-programmed cell death protein 1 (PD-1) and anti-programmed death-ligand 1 (PD-L1) antibodies are novel immunotherapies.
• These therapies show higher efficacy in tumors with significant somatic mutations, such as melanoma and non-small cell lung carcinoma.

Purpose of the Study:

• To hypothesize that high tumor mutational heterogeneity is crucial for the effectiveness of immune checkpoint-targeting therapies.

Main Methods:

• Literature review and hypothesis formulation based on existing clinical data.

Main Results:

• Elevated response rates to anti-PD-1/PD-L1 therapies correlate with high tumor mutational burden.
• Tumors like melanoma and non-small cell lung carcinoma, known for high mutation levels, exhibit better responses.

Conclusions:

• High levels of tumor mutational heterogeneity are proposed as a key factor driving the success of anti-PD-1/PD-L1 immunotherapies.