- A study, led by researchers at Stanford University School of Medicine, CA, has recently found an unexpected link between tuberculosis (TB) and cancer.
- The research suggests similarities in the immune responses in both cancer and TB infection.
- The results reveal fresh clues that may one day expand the therapeutic approach to treating TB infections.
“TB is still difficult to treat and kills nearly 1.5M people a year. Our work finds striking similarities between granulomas and the tumor microenvironment suggesting that immune evasion in cancer and TB significantly overlap.”
This is what Dr. Michael Angelo, an assistant professor of pathology, wrote on Twitter while explaining his new co-study which appears in the journal Nature Immunology. The study, led by graduate student Erin McCaffrey, employed an imaging technique to map the location of a number of immunosuppressive proteins in tissues from patients with TB, an infectious disease caused by Mycobacterium tuberculosis.
Asking an important question
In earlier research, the scientists discovered that clumps of white blood cells — called granulomas — in the lungs of individuals with active TB infection are packed with similar proteins that reduce the body’s immune response to infections or cancer cells.
Therefore, this made them wonder “whether TB granulomas and tumors share similar immunosuppressive properties.”
“If true,” the scientists told Medical News Today, “this would open up a whole realm of immunotherapeutic possibilities for treating TB that have been developed for cancer immunotherapy.”
Simply put: might the therapies used in treating cancers be potentially employed in treating TB infections?
To answer this question, the scientists decided to study a cohort of actively infected human tissues. Tissue samples were obtained from individuals who were treated for TB in the United States or South Africa.
The South African group consisted of pulmonary samples from people undergoing surgery for advanced TB, while a portion of the U.S. samples was from postmortem autopsy lung tissues of individuals with fatal TB.
In addition to the lung samples, the scientists also collected tissue samples from lymph nodes, endometrium, and pleural cavity from the U.S group. The researchers did this to “characterize TB infection at an earlier stage and assess how granuloma composition varies with infection site.”
Finally, all the samples were screened and assessed — using the novel imaging technique — for the presence of specific biomarkers that the scientists set out to investigate.
A ‘crucial’ discovery
In the study of the relationship between granuloma composition and organ site, the researchers report that the “vast majority of subsets occurred in similar proportions irrespective of organ site.”
Additionally, they also observed high levels of two proteins — PD-L1 and IDO1 — in the granuloma samples. These proteins can suppress the immune response to cancer and are found in the tumor tissues of certain types of cancers.
In blood sample studies collected from a large population of individuals living with TB, the researchers discovered that blood levels of PD-L1 correlated with clinical symptoms. Asymptomatic individuals had lower levels of PD-L1 in their blood and a lesser risk of developing an active infection when compared to individuals with higher levels of PD-L1.
Furthermore, the authors also discovered that individuals who were considered cured after TB treatment had significantly reduced blood levels of PD-L1 in comparison to people who were not cured.
Crucially, their results also suggested that macrophages — which are immune cells — might be the central determinants of immune response success or failure during TB disease.
In particular, the researchers noted that macrophages were responsible for producing the observed high levels of PD-L1 and IDO1, alongside the protein TGF-beta, which is also responsible for regulating the body’s immune response.
Surprisingly, they also found evidence suggesting that macrophages in TB granulomas prevent the activation of T cells. T cells are immune cells that protect the body against infections and also help in fighting cancer.
Reaction to the study
Some of the researchers’ findings concur with the authors of another paper that previously looked at T cell functions within tuberculosis granulomas.
On Twitter, Benjamin Henry Gern, M.D., senior author of that study explained that the new Stanford study had “a wealth of information and valuable insights.”
In addition, he noted that the new study corroborates what scientists have seen with “TGF-beta signaling in mice and [non-human primates].” Dr. Gern is acting assistant professor at Seattle Children’s Hospital in Washington.
Despite these positive reviews, the study is not without its limitations.
The study authors revealed to MNT that their study focused on individuals with symptomatic active disease. As a result, “they represent a small facet of the broad diversity of TB, both at the patient and granuloma level.”
The scientists also explained that due to limitations of their sample size, they do not know “how many bacteria are in each granuloma or how old the granulomas are,” pointing out that these are “important metrics in understanding the ‘success’ or ‘failure’ of the granuloma.”
They, however, added that these do not reduce the validity of their findings.
In concluding commentary, the study authors revealed to MNT that they plan to conduct future studies to address these limitations.
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