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Clinical Laboratories and Pathology Groups

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Clinical Laboratories and Pathology Groups

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Texas Researchers Find ‘Acid Walls’ That Shield Cancer Tumors from Body’s Immune System Response

Discovery could lead to new  treatments for cancer and tumors, but probably not to any new diagnostic assays for clinical laboratories

Researchers at the University of Texas Southwestern (UTSW) Medical Center have reported discovery of “acid walls” that appear to protect various types of cancer tumors from attack by the body’s immune system cells. Though the discovery is not directly related to a biomarker for a clinical laboratory diagnostic test, the basic research will help scientists develop ways to address the tumor’s acid wall strategy for defeating the immune system.

The UT scientists made their discovery using an internally developed imaging technique that employs nanoparticle probes to detect levels of acidity in cells. The research, they suggest, “could pave the way for new cancer treatment approaches that alter the acidic environment around tumors,” according to a UTSW press release.

Study leader Jinming Gao, PhD, Professor in the Harold C. Simmons Comprehensive Cancer Center and in the Departments of Biomedical Engineering, Cell Biology, Otolaryngology-Head and Neck Surgery, and Pharmacology at UT Southwestern, leads the Gao Lab which developed the nanoparticle technology.

The researchers published their study, titled “Severely Polarized Extracellular Acidity around Tumour Cells,” in the journal Nature Biomedical Engineering.

“This study revealed a previously unrecognized polarized extracellular acidity that is prevalent around cancer cells,” said lead study author Jinming Gao, PhD (above), Professor in the Harold C. Simmons Comprehensive Cancer Center and head of the Gao Lab at UT Southwestern Medical Center, in a press release. Gao believes the study “will lead to several new lines of research, such as studies to better understand how cancer cells polarize their acid excretion, how those cells can withstand the acidity level that kills CD8+ T cells, and how to inhibit acid excretion to allow T cells to better kill cancer cells,” the press release notes. (Photo copyright: University of Texas.)

Developing Acid Walls

As explained in the press release, scientists have long known that cancer cells are slightly more acidic than most healthy tissue. Gao and his team designed a nanoparticle known as pegsitacianine—a pH-sensitive fluorescent nanoprobe for image-guided cancer surgery—that disassembles and lights up when exposed to the acidic conditions in tumors.

However, “it was unclear why these nanoparticles fluoresced since a tumor’s acidity was thought to be too mild to trigger their activation,” the press release note.

To learn more, they used nanoparticle probes to illuminate a variety of individual cancer cells sampled from humans and mice, including lung, breast, melanoma, and glioblastoma, as well as tumor tissue. They discovered that the cancer cells secreted lactic acid—a waste product of digested glucose—at higher levels than previously known. The cells “pumped” the acid away from their malignant neighbors to form a protective “acid wall” around the tumor, the researchers noted in Nature Biomedical Engineering.

“Samples from human tumors showed that this acid wall was practically devoid of CD8+ T cells within the tumors, an immune cell type known to fight cancer,” the press release states. “When the researchers grew cancer cells and CD8+ T cells together in petri dishes that had been acidified to a 5.3 pH, the cancer cells were spared while the CD8+ T cells perished within three hours, suggesting that this severe acidity might thwart immune cell attack without harming the cancer cells.”

Gao’s team previously discovered that sodium lactate, the “conjugate base of lactic acid” as they describe it, increases the longevity of T cells and thus enhances their cancer-fighting capabilities. The researchers described the two molecules—lactate and lactic acid—as “Dr. Jekyll and Mr. Hyde,” and suggested that future therapies could seek to convert lactic acid to lactate.

“Gao noted that this discovery will lead to several new lines of research, such as studies to better understand how cancer cells polarize their acid excretion, how those cells can withstand the acidity level that kills CD8+ T cells, and how to inhibit acid excretion to allow T cells to better kill cancer cells,” the press release states.

Commercializing the Technology

Pegsitacianine was designed to aid cancer surgeons by illuminating the edges of solid metastatic tumors in real time during surgery, a 2023 UTSW Medical Center press release explains. About 24 hours prior to surgery, nanoprobes are delivered via IV. Then, the surgeon uses a near-infrared camera to visualize the cells.

UTSW has licensed pegsitacianine to OncoNano Medicine, a Dallas-area biotech startup launched to commercialize technologies from Gao Lab. Gao and his colleague Baran Sumer, MD, Professor and Chief of the Division of Head and Neck Oncology in UT Southwestern Medical Center’s Department of Otolaryngology and co-author on the study, both sit on OncoNano’s advisory board.

In January 2023, OncoNano announced that pegsitacianine had received Breakthrough Therapy Designation for Real-Time Surgical Imaging from the US Food and Drug Administration (FDA), which will fast-track the technology for development and regulatory review.

In a Phase II clinical trial published in the Annals of Surgical Oncology, the researchers tested the technology as part of cytoreductive surgery in patients with peritoneal metastases. However, a November 2023 UTSW press release noted that the technology is “tumor-agnostic and could potentially be used in other forms of cancer.” It is currently ready for Phase 3 trials, according to the OncoNano website.

More research and studies are needed to better understand this dynamic of cancer cells. Collectively, this research into cancer by different scientific teams is adding new insights into the way tumors originate and spread. At this time, these insights are not expected to lead to any new diagnostics tests that pathologists and clinical laboratories could use to detect cancer.

—Stephen Beale

Related Information:

UTSW Discovers Protective ‘Acid Wall’ Formed by Cancer Cells

Scientists Discover How Cancer Creates ‘Acid Wall’ Against Immune System

Severely Polarized Extracellular Acidity around Tumour Cells

Fluorescent Nanoprobe Produces ‘Breakthrough’ for Peritoneal Metastases

Pegsitacianine Informs Surgery in Peritoneal Carcinomatosis

Healthcare Experts Say Consumers Are Ready for Self-Test Flu Kits, But Are Physicians and Clinical Laboratories Ready to Let That Cat Out of the Bag?     

Clinical laboratories could play a key role in helping users collect their samples correctly, interpret results, and transfer flu test data to their health records

Clinical laboratories may have another opportunity to provide service to their clients and the physicians who treat them. With the success of at-home COVID-19 testing, consumer demand for self-tests is changing and advances in diagnostic technology now make it feasible to make more influenza (flu) tests available for consumers to buy and use at home.

At-home tests for SARS-CoV-2 can be found at pharmacies all across America. But that’s not the case with tests for influenza.

Should self-test flu kits eventually become available and common, clinical laboratories could offer the service of helping consumers understand:

  • that the test was conducted correctly (specimen collection and analysis),
  • that the result is accurate and reproducible, and
  • how to understand the results.

Clinical laboratories also could collect and input the results into their laboratory information system (LIS), then send those results to the patients’ electronic health record (EHR) at their physician’s clinic.

Christina Yen, MD

“Home flu testing would ensure that those who do need and receive antiviral medication for influenza are the ones who need it the most,” and that “we are making our treatment decisions based on data,” infectious disease specialist Christina Yen, MD (above), University of Texas Southwestern Medical Center, told STAT News. At-home flu self-tests could also bring opportunities for clinical laboratories to provide service to healthcare consumers and the physicians who treat them. (Photo copyright: UT Southwestern Medical Center.)

Pros and Cons of Consumers Doing At-home Influenza Testing

According to the federal Centers for Disease Control and Prevention (CDC), COVID-19 and influenza are both upper respiratory illnesses with similar symptoms. So, why don’t we have more at-home flu tests available? Partly because at-home testing is a relatively new phenomenon in modern healthcare.

“It’s really rare, and it’s really new that people are allowed to know about what’s happening inside their body without a physician in the middle,” Harvard epidemiologist Michael Mina, MD, PhD, told STAT News. The article uses the example of at-home pregnancy tests. Despite a prototype for an at-home pregnancy test being created in 1967, it took another decade before an over-the-counter pregnancy test became available to the public.

“The general thinking was, ‘How could a woman possibly know what to do if she found out she was pregnant on her own without a doctor in the room?’ That is a ridiculous concern because women have been doing that for millions of years,” Mina added.

So, why be cautious when it comes to giving patients the option of at-home flu testing?

There are some cons to at-home influenza tests. Average citizens are not clinical laboratory professionals. They might obtain too little sample for an accurate reading or read the results incorrectly. Then, there is the possibility for false-negatives or false-positives.

An at-home test user is not likely to consider the possibility of a false result, however clinicians look at the situation with more nuance. If the patient was still symptomatic or in a high-risk community, the provider could administer a more sensitive medical laboratory test to confirm the previous test results.

There are other concerns about at-home testing as well. Another STAT News article titled, “Growing Use of Home COVID-19 Tests Leaves Health Agencies in the Dark about Unreported Cases,” reported on a superspreading event that health officials did not know about: a Phish concert on Halloween.

“In a Facebook post from mid-November with hundreds of responses, concertgoers compared symptoms and positive test results, many of those from tests taken at home. But those data weren’t added to state public health tallies of COVID’s spread,” STAT News noted.

The larger concern is that samples obtained by at-home self-test users are not submitted for genomic sequencing. This could lead to incomplete data and delay identifying new variants of the coronavirus in communities.

“If nobody’s reporting the tests, are we really getting the information we need?” Atul Grover, MD, PhD, Executive Director of the Association of American Medical Colleges Research and Action Institute, told STAT News. “We have no idea what the true positivity rate is.”

Another barrier to at-home flu testing is that rapid influenza diagnostic testing can be unreliable. In 2009, the rapid influenza tests could only detect the H1N1 influenza virus in a mere 11% of samples, STAT News reported. Because of this, the FDA now requires manufacturers to test their rapid tests against eight different strains that change every year depending upon which strains are prevalent. This could present a problem if individuals use leftover tests from the previous flu season.

Do Pros of At-home Testing Outweigh the Cons?

At-home testing is convenient and makes testing more accessible to patients who may not be able to get to a clinic. Being able to test at home also encourages individuals to take precautions necessary to stop the spread of whichever illness they may have. Given the similarities in symptoms between influenza and COVID-19, people could benefit from having tools at home that correctly identify their illness.

At-home COVID-19 tests are here to stay, and at-home influenza tests may be on the way soon. Clinical laboratories could play an important role in educating the public on the correct handling of these tests.

Ashley Croce

Related Information:

Why Doesn’t the U.S. Have At-Home Flu Tests?

What Is the Difference between Influenza (Flu) and COVID-19?

We Still Don’t Have At-Home Testing for the Flu—But COVID-19 Has Changed the Stakes

Growing Use of Home COVID-19 Tests Leaves Health Agencies in the Dark about Unreported Cases

3D Imaging of Cancer Cells Could Lead to Improved Ability of Pathologists and Radiologists to Plan Cancer Treatments and Monitor Cell Interactions

New technology from researchers at the University of Texas Southwestern Medical Center enables the ability to study cancer cells in their native microenvironments

Imaging research is one step closer to giving clinicians a way to do high-resolution scans of malignant cells in order to diagnose cancer and help identify useful therapies. If this technology were to prove successful in clinical studies, it might change how anatomic pathologists and radiologists diagnose and treat cancer.

Researchers at the University of Texas Southwestern Medical Center developed a way to create near-isotropic, high-resolution scans of cells within their microenvironments. The process involves utilizing a combination of two-photon Bessel beams and specialized filtering. (more…)

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