Similar to aging, cancer is a state where cells lose their original identity. By applying age-reversal technologies, cancer cells can be forced to become normal again or even self-destruct, offering a novel approach to cancer treatment.

Despite both being keratinocyte-derived skin cancers, basal cell carcinoma (BCC) responds much less robustly to immunotherapy than cutaneous squamous cell carcinoma (CSCC). The pathologic complete response rate to perioperative PD-1 inhibition in BCC is only 23%, less than half the 51% seen in CSCC, highlighting their distinct immunobiology.

When you're injured, the cells that are "fittest" to repair the wound are those that divide fastest. This process inadvertently selects for cells that have acquired mutations promoting rapid growth—a key trait of cancer. Essentially, healing selects for potentially dangerous cells.

A major concern with age-reversal is its potential effect on cancer. However, research shows that de-aging cancer cells does not make them more aggressive. Instead, restoring youthful cellular information seems to inhibit their growth or kill them outright.

Cellular senescence is a biological process that permanently halts cell division. Contrary to being just a sign of aging, its primary function is to prevent damaged cells from becoming cancerous. It's a protective measure that stops unchecked proliferation when a cell cannot repair its own damage or undergo programmed cell death.

Nonmelanoma skin cancers' sensitivity to checkpoint inhibitors is due to high tumor mutational burden (TMB) caused by chronic UV light damage. This high TMB creates numerous neoantigens, which the immune system can effectively target once immunotherapy reverses immune suppression.

Unlike in lung cancer, PD-L1 expression levels do not guide treatment for nonmelanoma skin cancers. Patients with low or even negative PD-L1 levels still show significant response to anti-PD-1 therapy, making the test an unhelpful discriminator for treatment decisions.

The high efficacy of checkpoint inhibitors in cutaneous squamous cell carcinoma is enabling a "de-escalation" strategy. Upfront systemic therapy can be so effective that it eliminates the need for subsequent morbid local treatments like extensive surgery or radiation, a major benefit for elderly patients.

CLL-associated immunosuppression dramatically increases the risk and aggressiveness of skin cancers. This risk is not mitigated by novel therapies, and in some cases, the secondary skin malignancy can become a greater threat to a patient's life than their underlying CLL.