Does patient age influence anti-cancer immunity?

Graham Pawelec

Geriatric oncology, important for the ever-increasing numbers of elderly cancer patients, has thus far focused primarily on tolerance to chemotherapy. With the advent of breakthrough immunomodulatory antibody treatments relying on the patient's own immune system to control the tumor, the issue of immunosenescence becomes extremely important. There is increasingly a valid concern that anti-cancer immunity may be compromised in the elderly due to (i) their low amounts of naïve T cells (potentially leading to holes in the repertoire for neoantigens), (ii) "exhaustion" of potentially tumor-specific memory T cells, and (iii) higher amounts of suppressive cells. Encouragingly, but only anecdotally, accumulated clinical experience suggests that advanced age does not result in poorer responses or greater toxicity in elderly patients treated with anti-CTLA-4 or anti-PD-1/PD-L1 antibodies. Here, I briefly contrast immune features of the elderly with the young, commonly referred to as "immunosenescence," and the influence of patient age on the outcome of checkpoint blockade. As newer agents are licensed, and new combinations tested, broader and more detailed studies focusing on the age question will be crucial and should be taken into consideration when designing clinical trials.