Reprogramming Melanoma Tumor Microenvironment by Intratumoral Flu Vaccine a

Melanoma is the fifth most common cancer and is the deadliest form of skin cancer. While new immunotherapies called “checkpoint inhibitors” have revolutionized treatment, only about 30% of patients experience long-lasting benefit. Many tumors create a hostile environment that shields cancer cells from the immune system by recruiting suppressive cells and exhausting the T cells that would otherwise attack the tumor.

We propose a novel combination approach using two existing treatments: an influenza (flu) vaccine injected directly into tumors and a drug that blocks a protein called BRD4. When flu vaccine is injected into tumors, it activates the immune system to go to the site of cancer cells. The BRD4-blocking drug removes the suppressive cells that normally protect the tumor and keeps T cells from becoming exhausted, allowing them to continue fighting.

Our research will test whether giving flu vaccine first, followed by the BRD4 drug, can reprogram the tumor environment to be allow the immune system to be more active and effectively clear cancer cells. We will measure tumor shrinkage, analyze the immune cells inside tumors, and determine whether this combination helps checkpoint inhibitors, a current class of medications used to treat melanoma, work better.

This approach is particularly promising because flu vaccines are already FDA-approved and widely available, and BRD4 inhibitors are being tested in cancer clinical trials. If successful, this combination could offer additional treatment options for melanoma patients who don’t respond to current immunotherapies, potentially providing a safe, accessible treatment strategy that could be rapidly translated to the clinic.