Dr. Olasunkanmi Omojokun, a researcher at the Purdue Institute for Cancer Research, has emphasised the critical role of sex-based differences in the immune response to bone marrow cancer, scientifically identified as multiple myeloma (MM).
His latest research sheds light on the differential expression of Toll-like receptor 7 (TLR7) in male and female MM patients and how these variations influence the effectiveness of folate-conjugated TLR7 agonist (FA-TLR7a) therapy—a novel immunotherapeutic agent for cancer management.
Speaking about this development with select media platforms, he disclosed, “Multiple myeloma remains a formidable challenge in oncology, with significant disparities in incidence and prognosis between men and women,” Dr. Omojokun stated.
“Our research aimed to unravel the immunological factors that contribute to these differences, particularly focusing on how TLR7 expression varies by sex and how this influences treatment response.”
His study revealed that TLR7, an innate immune receptor crucial for recognizing single-stranded RNA viruses and activating type I interferon responses, is expressed at higher levels in female MM cells compared to male counterparts.
Similarly, plasmacytoid dendritic cells, which host TLR7, are more abundant in females than in males. He attributed this to the presence of XX chromosomes in females, as opposed to XY in males.
“This disparity suggests that women may have a more robust innate immune response, potentially explaining their better prognosis in various cancers, including multiple myeloma,” he noted.
Using an immunocompetent mouse model, his team investigated the therapeutic impact of FA-TLR7a, a novel immunotherapy designed to enhance anti-tumor immunity.
“We injected MM cells into male and female mice, treated them with FA-TLR7a, and observed significant differences in tumor progression and immune activation,” Dr. Omojokun explained.
The results were striking. Female mice exhibited a stronger response to FA-TLR7a, with reduced tumor burden, decreased bone metastasis, and enhanced immune cell activation.
“We found that the treatment was more effective in females, leading to better tumor suppression and less bone destruction,” he stated.
Dr. Omojokun highlighted the clinical significance of these findings, emphasizing the need for sex-specific approaches in MM treatment.
“If we can harness these biological differences, we may be able to develop more effective, personalized therapies for both men and women,” he said.
Beyond tumor suppression, his research also explored the impact of FA-TLR7a on immune cell populations within the bone marrow.
“We observed an increase in activated immune cells, particularly those involved in tumor surveillance and destruction, in the female treatment group,” he noted.
One of the key discoveries was the alteration in immunoglobulin G2b (IgG2b) levels, which play a role in immune response modulation.
“Females treated with FA-TLR7a showed a significant shift in IgG2b expression, suggesting a stronger and more sustained immune activation,” Dr. Omojokun revealed.
He also discussed how bioluminescence imaging helped visualize tumor localization and metastasis, showing that male mice had a higher tendency for widespread bone involvement.
“Our imaging studies confirmed that untreated males exhibited more aggressive disease progression, reinforcing the need for targeted interventions,” he said.
Additionally, his study used micro-computed tomography (µCT) to assess bone integrity and osteolysis in MM-bearing mice.
“We observed more severe bone loss in untreated males, especially at the trabecular region of the tibia, whereas FA-TLR7a treatment significantly preserved bone structure, particularly in female mice,” he pointed out.
Dr. Omojokun eemphasised hat his findings could pave the way for sex-specific cancer immunotherapies.
“Most cancer treatments are designed as one-size-fits-all, but our research shows that sex differences matter. A more tailored approach could improve patient outcomes, as we observed a 69% therapeutic response in males compared to 83% in females,” he stated.
He urged further investigations into the molecular mechanisms underlying TLR7 expression differences between sexes.
“We need to determine whether hormonal influences, genetic factors, or epigenetic modifications contribute to these disparities,” he explained.
As he concluded his discussion with journalists, Dr. Omojokun underscored the broader implications of his research.
“If we can refine immunotherapies based on sex-specific immune responses, we may revolutionize treatment not just for multiple myeloma but for other cancers as well,” he asserted.
“This is just the beginning. There’s still much to uncover, but we now have a clear direction for future studies,” he said with conviction.
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