The UC Davis Comprehensive Cancer Center has made a groundbreaking discovery that may explain why certain immune cells in humans are less effective at fighting solid tumors compared to non-human primates. This finding could lead to more powerful cancer treatments.

Researchers have uncovered an evolutionary change that makes the Fas Ligand (FasL) protein, essential for triggering programmed cell death and killing cancer cells, vulnerable to being disabled by plasmin in humans. This genetic mutation is unique to humans and not found in non-human primates, such as chimpanzees.

“The evolutionary mutation in FasL may have contributed to the larger brain size in humans,” said Jogender Tushir-Singh, senior author for the study and an associate professor in the Department of Medical Microbiology and Immunology. “But in the context of cancer, it was an unfavorable tradeoff because the mutation gives certain tumors a way to disarm parts of our immune system.”

The team discovered that a single evolutionary amino acid change – serine instead of proline at position 153 – makes FasL more susceptible to being cut and inactivated by plasmin. Plasmin is often elevated in aggressive solid tumors, such as triple negative breast cancer, colon cancer, and ovarian cancer.

This means that even when human immune cells are activated and ready to attack the tumor cells, one of their key death weapons – FasL – can be neutralized by the tumor environment, reducing the effectiveness of immunotherapies. The findings may help explain why CAR-T and T-cell-based therapies often fall short in solid tumors.

Blood cancers often do not rely on plasmin to metastasize, whereas tumors like ovarian cancer heavily rely on plasmin to spread the cancer.

Significantly, the study also showed that blocking plasmin or shielding FasL from cleavage can restore its cancer-killing power. This finding may open new doors for improving cancer immunotherapy.

By combining current treatments with plasmin inhibitors or specially designed antibodies that protect FasL, scientists may be able to boost immune responses in patients with solid tumors.

“Humans have a significantly higher rate of cancer than chimpanzees and other primates,” said Tushir-Singh. “There is a lot that we do not know and can still learn from primates and apply to improve human cancer immunotherapies.”

A groundbreaking clinical trial has revealed that a single dose of psilocybin, a naturally occurring psychedelic compound found in mushrooms, can provide sustained reductions in depression and anxiety in individuals with cancer suffering from major depressive disorder. The findings, published in the peer-reviewed journal CANCER, suggest that this treatment approach may offer long-term relief for cancer patients struggling with depression.

The study involved 28 participants who received psychological support from a therapist prior to, during, and after receiving a single 25-mg dose of psilocybin. Two years later, a significant proportion of these individuals demonstrated lasting reductions in depression and anxiety. Specifically:

* 53.6% (15 patients) showed a sustained reduction in depression.
* 50% (14 patients) experienced remission from depression as well as reduced anxiety.
* 42.9% (12 patients) reported reduced anxiety at the two-year mark.

Building on these promising results, an ongoing randomized, double-blind trial is currently evaluating up to two doses of 25 mg of psilocybin versus placebo for treating depression and anxiety in cancer patients. This study aims to determine whether repeating the treatment can resolve depression for more than half of the participants.

According to lead author Manish Agrawal, MD, from Sunstone Therapies, “One dose of psilocybin with psychological support has a long-term positive impact on relieving depression for as much as 2 years for a substantial portion of patients with cancer. If randomized testing shows similar results, this could lead to greater use of psilocybin to treat depression in patients with cancer.”

A new study has made a groundbreaking discovery in the treatment of glioblastoma, a type of brain cancer with few effective treatments available. Researchers from Keck Medicine of USC have found that combining Tumor Treating Fields (TTFields) therapy with immunotherapy and chemotherapy can significantly extend survival rates among patients diagnosed with glioblastoma.

Glioblastoma is a highly aggressive form of brain cancer, with an average survival rate of only eight months. The National Brain Tumor Society reports that the prognosis for glioblastoma remains poor, even with aggressive treatment. However, this new study has shown promising results, demonstrating a 70% increase in overall survival when TTFields are used alongside immunotherapy and chemotherapy.

TTFields work by delivering targeted waves of electric fields directly into tumors to stop their growth and signal the body’s immune system to attack cancerous tumor cells. This approach is particularly effective for glioblastoma, as it disrupts the tumor’s ability to evade the immune response.

In this study, patients who received TTFields combined with chemotherapy and immunotherapy lived approximately 10 months longer than those who had used the device with chemotherapy alone in the past. Those with large, inoperable tumors showed an even stronger immune response to TTFields, living approximately 13 months longer compared to patients who underwent surgical removal of their tumors.

The lead researcher on this study, Dr. David Tran, a neuro-oncologist at Keck Medicine, explained that by using TTFields with immunotherapy, the body is “primed” to mount an attack on the cancer, enabling the immunotherapy to have a meaningful effect in ways it could not before. This approach represents a significant breakthrough in the treatment of glioblastoma.

This study demonstrates that combining TTFields with immunotherapy triggers a potent immune response within the tumor – one that ICIs can then amplify to bolster the body’s own defense against cancer. “Think of it like a team sport – immunotherapy sends players in to attack the tumor (the offense), while TTFields weaken the tumor’s ability to fight back (the defense),” Dr. Tran explained.

The findings of this study have significant implications for the treatment of glioblastoma and offer new hope for patients who previously had limited options. Further studies are needed to determine the optimal role of surgery in this setting, but these results may offer a glimmer of light for those affected by this devastating disease.

As Dr. Tran noted, “Further studies are needed to determine the optimal role of surgery in this setting, but these findings may offer hope, particularly for glioblastoma patients who do not have surgery as an option.” The multicenter Phase 3 clinical trial is currently underway at 28 sites across the United States, Europe, and Israel, with over 740 patients expected to be enrolled through April 2029.