Does the Immune System Naturally Protect Against Cancer?

The importance of the immune system in conferring protection against pathogens like viruses, bacteria, and parasitic worms is well established. In contrast, there is a long-lasting debate on whether cancer prevention is a primary function of the immune system. The concept of immunological surveillance of cancer was developed by Lewis Thomas and Frank Macfarlane Burnet more than 50 years ago. We are still lacking convincing data illustrating immunological eradication of precancerous lesions in vivo. Here, I present eight types of evidence in support of the cancer immunosurveillance hypothesis. First, primary immunodeficiency in mice and humans is associated with increased cancer risk. Second, organ transplant recipients, who are treated with immunosuppressive drugs, are more prone to cancer development. Third, acquired immunodeficiency due to infection by human immunodeficiency virus (HIV-1) leads to elevated risk of cancer. Fourth, the quantity and quality of the immune cell infiltrate found in human primary tumors represent an independent prognostic factor for patient survival. Fifth, cancer cells harbor mutations in protein-coding genes that are specifically recognized by the adaptive immune system. Sixth, cancer cells selectively accumulate mutations to evade immune destruction (“immunoediting”). Seventh, lymphocytes bearing the NKG2D receptor are able to recognize and eliminate stressed premalignant cells. Eighth, a promising strategy to treat cancer consists in potentiating the naturally occurring immune response of the patient, through blockade of the immune checkpoint molecules CTLA-4, PD-1, or PD-L1. Thus, there are compelling pieces of evidence that a primary function of the immune system is to confer protection against cancer.