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Lung Cancer News
Mar. 15, 2023 — A new study represents a first step towards generating highly detailed 3-dimensional maps of lung tumors using genetically engineered mouse ...
Mar. 13, 2023 — Scientists have discovered why breast cancer cells that have spread to the lungs may 'wake up' following years of sleep -- forming incurable secondary tumors. Their research reveals the ...
Feb. 13, 2023 — Researchers show how stimulating dendritic cells through certain pathways produces strong T cell activity against tumors and works in conjunction with immune checkpoint inhibitors to produce even ...
Feb. 1, 2023 — New data from a clinical trial shows improved rates of survival and reduced risk of recurrence in patients taking osimertinib, a targeted therapy for non-small cell lung cancer ...
Jan. 9, 2023 — A new study found that deleting a gene called KMT2D caused normal (basal) lung cells grown in complex cultures called organoids to transform into lung squamous carcinoma (LUSC) ...
Jan. 4, 2023 — A research team has shown that Sarunashi juice and its constituting component isoquercetin help prevent and reduce lung cancer in laboratory ...
Dec. 26, 2022 — Researchers report that they have developed a new experimental pipeline to combine bacterial therapy with current cancer drugs. Their study, which explores resistance to bacterial therapy at the ...
Dec. 1, 2022 — About 80% of people with cancer suffer from significant muscle wasting, or loss of muscle tissue, and 30% of these patients die from this condition. New research in mice finds that the severity of ...
Nov. 29, 2022 — While it may seem common knowledge that smoking is bad for your lungs, if and how ultrafine particles present in cigarette smoke impact the development and progression of lung cancer remains unclear. ...
Nov. 15, 2022 — Airway inflammation and emphysema are more common in marijuana smokers than cigarette smokers, according to a new study. Researchers said the difference may be due to the way that marijuana is smoked ...
Nov. 8, 2022 — Scientists investigating the mechanics of the early stages of lung cancer have identified a new potential treatment, which could also aid early detection of the disease. Levels of a key protein -- ...
Oct. 25, 2022 — A new study has revealed significant racial disparities in how quickly minorities with the most common form of lung cancer receive potentially lifesaving radiation therapy compared with their white ...
Oct. 6, 2022 — This year, about 200,000 people will be diagnosed with non-small-cell lung cancer, the second leading cause of death after cardiovascular disease. Researchers are working to improve the odds for ...
Sep. 28, 2022 — Despite significant advances, mortality from brain tumors remains high with five-year survival rates of 36%. More accurate diagnoses might improve the situation, but tissue biopsies are invasive and ...
Sep. 21, 2022 — The majority of the socioeconomic disparity, or deprivation gap, in cancer incidence could have been prevented in England between 2013 and 2017 if nobody had smoked, according to a new ...
Sep. 16, 2022 — In Germany, about ten per cent of all children are born before the 37th week of pregnancy and are thus considered premature. Many of these premature babies require help with breathing due to their ...
Sep. 13, 2022 — Researchers used extensive single-cell analysis to create a spatial map of tumor-infiltrating B cells and plasma cells in early-stage lung cancers, revealing new roles for these immune cells in ...
Sep. 13, 2022 — A new mechanism has been identified through which very small pollutant particles in the air may trigger lung cancer in people who have never smoked, paving the way to new prevention approaches and ...
Sep. 1, 2022 — About 30,000 cases of lung cancer occur in Spain each year. Mutations in KRAS oncogenes account for 10-15% of these cases, a subgroup against which there are still no effective therapies. Researchers ...
Aug. 31, 2022 — An experimental combination of two drugs halts the progression of small cell lung cancer, the deadliest form of lung cancer, according to a study in ...
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Study Finds Senescent Immune Cells Promote Lung Tumor Growth
Macrophages are a type of white blood cell that are among the body's first line of defense against infection. In addition to killing harmful microorganisms, macrophages typically can initiate a response against tumors. However, macrophages, like other cells, can enter a state called senescence, which is linked to aging, disease and multiple physiological problems.
When cells become senescent, they stop dividing, but they do not die and are not always eliminated from the body. They can linger and accumulate in tissues and may secrete molecules that are harmful. This is why senescent cells have been called "zombie cells." The reason why healthy cells become senescent is not well understood.
In new Cancer Cell study, researchers discovered senescent macrophages in the lung that not only lingered but also promoted tumor growth.
"Conceptually, the idea that a macrophage can become senescent and be tumor-promoting is unexpected," says Darren Baker, Ph.D., a Mayo Clinic senescent cell biologist and senior author of the study. "This finding brings us one step closer to better understanding how tumors and cancer form at the cellular level."
Dr. Baker and his colleagues found that senescent macrophages appear to block the immune system from being able to respond to and eliminate the abnormal growth of cells. This leads to a tumor.
"Through different experiments and analyses, we could distinguish those senescent macrophages from the other macrophages. We found that if we eliminate them, through genetic or pharmacological approaches, we delay tumor formation," says lead author Luis Prieto, Ph.D., a postdoctoral fellow and recent graduate of the Mayo Clinic Graduate School of Biomedical Sciences.
The researchers reasoned that precancerous cells communicated with the surrounding cells, including macrophages, and triggered the macrophages to become senescent. In turn, the senescent cells then appeared to alter the surrounding area in a way that promoted tumor growth.
Initially, the researchers thought removing the senescent cells would result in more adenomas, the type of lung tumor studied. But the results of their early experiments showed otherwise.
"It was very challenging, because every time we would do an experiment, it was just the opposite of what we'd expect," Dr. Prieto says. "If one removes tumor suppressors regulating senescent cells, one would expect to have more tumors, but it actually just happened to have the opposite results. There were fewer tumors in the absence of those tumor suppressors."
The researchers worked with study co-author Hu Li, Ph.D., an individualized medicine researcher at Mayo Clinic, and conducted single-cell RNA sequencing in his lab. This work helped them identify lung macrophages as a key cell type driving tumor growth. Now, they believe the macrophages are responding to the precancerous cells as they begin to cause tumors.
"We had to rethink our initial ideas as we learned a lot more about what cells can do. Then, it started to make a lot more sense about how senescent macrophage cells can influence other cells, the environment and the immune system in this case," Dr. Baker says.
A complementary paper by researchers based in the U.K. Was also published in the journal Cancer Cell.
More information: Luis I. Prieto et al, Senescent alveolar macrophages promote early-stage lung tumorigenesis, Cancer Cell (2023). DOI: 10.1016/j.Ccell.2023.05.006
Scott Haston et al, Clearance of senescent macrophages ameliorates tumorigenesis in KRAS-driven lung cancer, Cancer Cell (2023). DOI: 10.1016/j.Ccell.2023.05.004
Citation: Study finds senescent immune cells promote lung tumor growth (2023, September 26) retrieved 23 October 2023 from https://medicalxpress.Com/news/2023-09-senescent-immune-cells-lung-tumor.Html
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How A Multi-Cancer Screening Test Would Play Out In The Clinic
Confirming an actual cancer diagnosis in patients flagged as potentially having a malignancy by a multicancer blood test typically required multiple imaging scans and laboratory tests, suggested results from PATHFINDER, a prospective U.S. Cohort study.
In a convenience sample of adults 50 and up with no signs or symptoms of cancer, the multicancer early detection (MCED) test picked up a cancer signal in 1.4%, with true positives identified in 0.5% via pathologic, laboratory, or radiographic confirmation, reported researchers led by Deb Schrag, MD, of Memorial Sloan Kettering Cancer Center in New York City.
In patients with a cancer signal detected, more than 90% underwent imaging (often multiple scans), over 80% received laboratory tests, and nearly half had a biopsy or other procedure as part of their diagnostic workup, with false positives ultimately identified in 0.9% of the cases.
The Galleri cell-free DNA test (developed by Grail), also led to false negatives in 1.3% of the more than 6,500 participants in the study, the researchers detailed in The Lancet.
"When the MCED assay was positive and cancer was present, the test accurately predicted the tumor origin, and half of all cancer diagnoses were made in less than 2 months," wrote Schrag and colleagues. "When cancer could not be confirmed, diagnostic assessments, often with serial scans, continued for a longer duration, typically extending for 4 months."
Many of the cancers detected -- including some at early stages -- would not have been covered by recommended screening tests, the researchers pointed out, with MCED identifying a tumor type without a U.S. Preventive Services Task Force (USPSTF) screening recommendation in 24 of the 35 true-positive cases.
"For example, cancers of the bile duct, small intestine, pancreas, and a spindle-cell neoplasm were detected at early stages amenable to surgical resection," the study authors noted. "These lethal malignancies are unlikely to have been identified upon routine physical examination or screening."
There is a considerable amount of "hype" for a blood test that could potentially reduce the complexities of established screening programs while also detecting additional cancer types, said Richard Lee, PhD, of the Institute of Cancer Research in London, and Hilary Robbins, PhD, of the International Agency for Research on Cancer in Lyon, France, writing in an accompanying editorial.
"The PATHFINDER results allow us to put numbers to some of these potential benefits of MCED testing, as well as the harms," the duo wrote.
On the positive front, the 35 patients diagnosed because of MCED testing "represent an important increase in earlier diagnosis," while adding that few invasive procedures were performed due to a false-positive result.
But the number of cancers diagnosed during the study by standard USPSTF guideline screening (n=29) was actually similar to those from the MCED test, Lee and Robbins pointed out. By their calculations, the assay had a "somewhat underwhelming" sensitivity of just 29%.
While studies like PATHFINDER are producing "exciting data," the editorialists said, concerns remain over "low sensitivity, overlap with existing, proven approaches, and unknown mortality benefit and cost-effectiveness," concluded Lee and Robbins.
"In the wider MCED setting, we must consider confidence in cancer detection versus exclusion, test convenience, testing frequency, and added value beyond existing screening approaches as well as primary cancer prevention," they added.
PATHFINDER was conducted at oncology and primary care outpatient clinics across seven U.S. Health networks and included participants age 50 years or above without signs or symptoms of cancer. A majority (56%) had an additional risk for cancer based on their smoking or cancer history, meeting guideline criteria from the National Comprehensive Cancer Network for germline testing, or due to a hereditary cancer syndrome.
Mean participant age was 63 years, nearly two-thirds were women, and the vast majority were white (91.7%). About a fourth had a previous cancer, and nearly all were up to date with cancer screening.
Of the 6,621 participants available for analysis, the MCED detected a cancer signal in 92, including 35 true positives (with six recurrences) and 57 false positives. In 97% of the true positives, the test correctly identified the primary cancer location. Fourteen of the 29 true positives (48%) that involved a new cancer diagnosis were stage I/II, including six solid tumors and eight hematologic malignancies.
After excluding two patients who developed clinical symptoms before their MCED results, imaging was performed in 92% of the 90 patients with a cancer signal detected and 53% had multiple imaging tests. Lab tests were performed in 84%. Median observed time to diagnostic resolution of a positive test was 79 days (57 days for the true positives and 162 days for the false positives).
Among the true positives, 82% underwent a procedure, as compared with 30% of the false positives. Surgeries were performed in 9% and 2% of the two groups, respectively.
Of the 6,529 negatives results with MCED, 6,235 were true negative, 86 false negatives, and 208 did not have a cancer status assessment at study end to determine whether it was true or false.
To detect a single new cancer, the number needed to screen with MCED was 189, Schrag's and colleagues determined, and the test had a specificity and negative predictive value of 99.1% and 98.6%, respectively.
Within the 12-month study period, a total of 122 cancers were diagnosed overall in 121 patients, including the 35 by MCED testing, 38 through screening, and 48 detected clinically.
The authors acknowledged several imitations to their study, including the fact that the findings may not be generalizable because of the lack of ethnic, racial, and socioeconomic diversity in the cohort, as well as due to the high rate of adherence to cancer screening.
Moreover, they said that volunteer bias could have influenced participants' risk or their preferences for undergoing comprehensive diagnostic assessments, and that the 12-month study period was short and that rates of later cancer diagnoses are uncertain.
Mike Bassett is a staff writer focusing on oncology and hematology. He is based in Massachusetts.
Disclosures
The study was funded by Grail.
Schrag reported relationships with JAMA and Grail. Study co-authors disclosed relationships with multiple industry entities and included Grail employees.
Lee reported relationships with the Royal Marsden Cancer charity, Cancer Research U.K., Innovate U.K. (co-funded by Roche), RM Partners Cancer Alliance, the National Institute for Health and Care Research (NIHR), NHS England, and Royal Marsden Private Care, and is the NHS England Joint National Clinical Lead for the Targeted Lung Health Check Programme and NIHR Clinical Research Network National Specialty Lead for Screening, Prevention, and Early Detection.
Robbins reported relationships with the National Cancer Institute, the Institut National du Cancer, the World Cancer Research Fund International, and the Lung Cancer Research Foundation.
Primary Source
The Lancet
Source Reference: Schrag D, et al "Blood-based tests for multicancer early detection (PATHFINDER): a prospective cohort study" Lancet 2023; DOI: 10.1016/S0140-6736(23)01700-2.
Secondary Source
The Lancet
Source Reference: Lee R, Robbins HA "PATHFINDER: another step on the uncharted path to multicancer screening" Lancet 2023; DOI: 10.1016/S0140-6736(23)02050-0.
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