The era of comic book superheroes began in the mid-1930s, but its defining moment came in 1938 when Clark Kent aka Superman entered the stage. With his incredible powers of x-ray vision, ability to fly faster than a speeding bullet, lethal strength and personal indestructibility, he was able to detect and destroy criminal activity before much harm was done. However, the bad guys figured out a way to block Superman’s crime-fighting abilities by exposing him to kryptonite, which turned him into a weakling. Thus, the tales were most exciting when Superman—made helpless by kryptonite and looking like all was lost—managed to find a way to protect himself from kryptonite and regain his superpowers.  

The immune system is our own body’s superhero, defending us against bad guys such as viruses and cancer tumors. As the National Institutes of Health tells us, “As part of its normal function, the immune system detects and destroys abnormal cells and most likely prevents or curbs the growth of many cancers.” However, like the scheming criminals in comic strips, cancer tumors develop “kryptonite” ways to weaken the immune system’s powers and get away with harm. One way is to become a cold tumor.

The National Cancer Institute describes such tumors as unlikely to trigger a strong immune system defense. “Cold tumors tend to be surrounded by cells that are able to suppress the immune response and keep T cells (a type of immune cell) from attacking the tumor cells and killing them. Cold tumors usually do not respond to immunotherapy.” Prostate cancer (PCa) is a cold tumor, along with cancers of the breast, ovary, pancreas and a specific brain cancer called glioblastoma.

Immunotherapy for prostate cancer

Drugs that harness the immune system against PCa are in a category called immunotherapy. One promising type is a class called immune checkpoint inhibitors (ICIs). You may have heard of brand names like Keytruda, Opdivo, and Imfinzi. They work by blocking “checkpoints” designed to hold the immune system in check.  Blocking them unleashes ICIs against PCa cells anywhere in the body.

However, there’s a delicate balance. Normal immune checkpoint inhibitors are important because they keep the immune system from losing control. If this happens, it generates autoimmune disorders that can harm any healthy organ. Imagine if Superman began using his powers indiscriminately. Sure, he’d get rid of crime, but in the process, he’d wreck Metropolis. Similarly, the challenge in using ICIs against PCa is developing ways to control their strength only for good, targeted efficiently against PCa.

A new approach to improve immunotherapy response

Researchers have developed a new approach help ICI immunotherapy become more successful without loss of control. It involves a type of “vaccine” that can outgun PCa defenses.^[i] Normally, when a hostile entity like a virus or cancer cell invades healthy cells, the cells under attack emit special signaling proteins called interferons. Interferons are named for their ability to interfere protectively against the invader and its ability to reproduce itself. Additionally, they also act as messages to the immune system, enrolling components like killer cells to come to the rescue, plus they can help generalize the immune response by broadening its recognition of similarly mutated invasive cells (remember that cancer cells can quickly mutate and become more aggressive). Altogether this powerful concerted defense is called a Type-I interferon (IFN-I) response, yet cold tumors can counteract this defense as soon as it begins.

Conducting experiments with mice that were implanted with cancer tumors, the researchers discovered a way to put the IFN-I response into turbo, right from the start. They developed a special type of vaccine to highly strengthen a very early IFN-I response, activating the superpower of the immune system’s cancer-destroying components, and generalizing (spreading) its ability to recognize any cellular mutations that the cancer tumor was developing.

The vaccine itself takes advantage of messenger molecules called mRNA. When specially encoded mRNA enters a cell, it can change the cell’s behavior. In this case, the vaccine is encoded to exponentially increase the IFN-I response in cold tumors.

According to a medical news alert, the results of defeating tumors in mice that were given the mRNA vaccine “achieved the promising results not by attacking a specific target protein expressed in the tumor, but by simply revving up the immune system — spurring it to respond as if fighting a virus. They did this by stimulating the expression of a protein called PD-L1 inside of tumors, making them more receptive to treatment.”

This is certainly exciting news for PCa patients, since theoretically tumors could be defeated as soon as they are detected with no further treatment necessary. Even more encouraging is the research team’s belief that this would apply to virtually any tumor cancer, engaging the body’s natural Superman to outfox the cancer’s “kryptonite” mechanisms. The possibilities still lie in the future, but this groundbreaking discovery certainly brings new hope in the present.

NOTE: This content is solely for purposes of information and does not substitute for diagnostic or medical advice. Talk to your doctor if you are experiencing pelvic pain, or have any other health concerns or questions of a personal medical nature.

References

[i] Qdaisat S, Wummer B, Stover BD, Zhang D et al. Sensitization of tumours to immunotherapy by boosting early type-I interferon responses enables epitope spreading. Nat Biomed Eng. 2025 Jul 18.