New and less expensive approach to digital PCR may improve cancer detection

Digital polymerase chain reaction (PCR) testing was initially proposed in the early 1990s, but as is so often the case, translating a concept into conventional medical practice is no mean feat. However, researchers in China have proposed a novel design for a digital PCR chip that overcomes several barriers to routine use, such as lengthy introduction times for sample media. This design is a self-priming chip with 6-plex detection capabilities provided by six detection areas across a four-layer structure, and the multiplex function is provided by pre-introduction of the specific reaction mix to a given detection area within the chip. This approach accelerates the multiplexing time thanks to avoidance of competition from the use of multiple primers in the same physical space, but this also cuts down on the need for reagents, a particularly salient feature in the world of the COVID-19 pandemic. However, this approach also cuts down on instrument cost as well as on the evaporation that plagues conventional PCR processing. The researchers tried this test for detection of five types of mutations of the epidermal growth factor receptor gene in 15 samples from lung cancer patients, and no significant differences in detection were observed for any of the test mutations. The authors said these chips can be stored for as long as two months at 4° C after lyophilization, making them a storable solution for many diagnostic needs, which could include disease monitoring and pathogen detection in addition to cancer diagnosis. These findings are spelled out in more detail in the Aug. 14, 2020, issue of ACS Nano.

Stromal cell subtypes identified in TNBC

Researchers at the Garvan Institute of Medical Research have used single-cell RNA sequencing to identify subtypes of cancer-associated fibroblasts (CAFs) in triple-negative breast cancer (TNBC). CAFs are part of the tumor microenvironment and were originally identified for their roles supporting tumors. More recent work, however, has suggested that they can have both pro-and antitumor effects, likely mediated by different subpopulations. The authors used single-cell sequencing of TNBC stromal cells and identified four subtypes, two that were CAF-like and two that were perivascular-cell like (PVL). Furthermore, they showed that “gene signatures from inflammatory-CAFs and differentiated-PVL cells in independent TNBC patient cohorts revealed strong associations with cytotoxic T-cell dysfunction and exclusion, respectively. Such insights present promising candidates to further investigate for new therapeutic strategies in the treatment of TNBCs.” Their work appeared in the Aug. 13, 2020, issue of the EMBO Journal.

Microbiome metabolites as immunotherapy adjuvants

Investigators at the University of Calgary have identified the metabolites responsible for microbiome effects on checkpoint blockade. Microbiome composition has been linked to the likelihood of responding to checkpoint blockade in cancer patients, and the authors investigated three species – Bifidobacterium pseudolongum, Lactobacillus johnsonii and Olsenella species – to understand how they might facilitate a response to checkpoint blockers. They demonstrated that the B. pseudolongum metabolite inosine could enter the systemic circulation due to enhanced gut barrier permeability after checkpoint inhibitor therapy, and activated antitumor T cells via inosine signaling at the adenosine A2A receptor. The authors concluded that “collectively, our study identifies a novel microbial metabolite-immune pathway that is activated by immunotherapy that may be exploited to develop microbial-based adjuvant therapies.” They published their work in the Aug. 14, 2020, issue of Science.

Pandemic significantly impeded breast cancer follow-up

The COVID-19 pandemic will go down in history as one of the most lethal of all health hazards, but it carries with it a series of subsidiary lethalities as well. Among these is the now-commonplace delays in cancer care, and a new journal article suggests that more than four in 10 of all breast cancer patients in the U.S. have experienced those delays. A questionnaire administered nationally drew more than 600 responses, and 63% confirmed that they were under care for a diagnosis of breast cancer. Of this group, 44% said they had experienced delays in care in connection with their cancer, with routine follow-up visits the most commonly deferred appointment at nearly 80%. However, 66% of respondents indicated that breast reconstruction surgery had been delayed while another 60% said diagnostic imaging services were held up due to the pandemic. Lab testing was delayed for half of those who had reported delays of any type, while radiotherapy (30%) and infusion therapy (32%) were commonly delayed as well. Surgical tumor excision was delayed in more than one in four respondents, but the authors remarked that the delays did not seem reflective of any deliberate approach to triage. Their results appear in the Aug. 9 issue of Breast Cancer Research and Treatment.