DNA damage, tumor mutational load and their impact on immune responses against cancer

Area of Science:

• Oncology
• Immunology
• Genetics

Background:

• Immunotherapy has revolutionized cancer treatment, with immune checkpoint inhibitors approved for several malignancies.
• Cancers like melanoma, lung, renal, and bladder carcinomas often exhibit high mutational loads.

Purpose of the Study:

• To review the mechanisms by which DNA damage contributes to increased mutational load and neoantigen formation.
• To discuss the potential exploitation of these mechanisms for improved cancer immunotherapy.

Main Methods:

• Literature review of studies on DNA damage, tumor mutational burden, neoantigens, and immunotherapy.
• Analysis of the relationship between genetic alterations and immune system recognition in cancer.

Main Results:

• High mutational load in certain cancers is linked to an increased number of tumor neoantigens.
• DNA damage is a key factor influencing mutational load and the generation of neoantigens.

Conclusions:

• Understanding the role of DNA damage in neoantigen formation is crucial for advancing cancer immunotherapy.
• Exploiting DNA damage-induced neoantigens offers promising strategies for future immunotherapeutic approaches.