Tag: skin cancer

Categories : CancerTags :

Memory Killer Cells can Improve Melanoma Survival

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Melanoma Cells. Credit: National Cancer Institute

In a study published in the journal Immunity, Researchers at Karolinska Institutet and the University of Copenhagen shown that high levels of memory killer cells in cancer tissue correlate with a better survival rate in people with melanoma.

Certain immune T cells called tissue-resident memory cells are formed locally in the skin and other tissue, and protect against infections that they have encountered before. Some of them express proteins that enable them to kill infected cells. These “memory killer cells” can also contribute to the inflammatory skin disorders vitiligo and psoriasis. Recent research has shown that they are also involved in the body’s immune response to various cancers.

Varying responses to treatment

The memory killer cells have been shown to respond to immunotherapy, a Nobel Prize-winning cancer therapy involving the tweaking/activation of the immune system. Immunotherapy is normally administered as a complement to other cancer treatments, and there is considerable variation in how patients respond to it.

“We don’t know so much about how and why memory killer cells are formed in the skin and what it means for cancer patients,” says Professor Yenan Bryceson at Karolinska Institutet. “Finding out how these cells develop enables us to contribute to the development of more efficacious immunotherapy for diseases like melanoma.”

The study charted the development of memory killer cells in human skin, performed as a collaborative effort between KI researchers Beatrice Zitti and Elena Hoffer. The researchers isolated T cells from the skin and blood of healthy volunteers and used advanced techniques to examine gene activity and expression of different proteins. This allowed them to identify T cells in the blood with the potential to develop into memory killer cells in skin or other tissues. After knocking out specific genes, they could also demonstrate which genes are required for the maturation of memory killer cells in tissue.

More effective immunotherapy

The researchers then went on to study tumour samples from melanoma patients and found that those with a higher rate of survival also had a larger accumulation of epidermal memory killer cells.

We’ve been able to identify several factors that control the formation of memory killer cells, which play an important part in maintaining a healthy skin,” says dermatologist Liv Eidsmo, professor at the University of Copenhagen in Denmark and researcher at Karolinska Institutet, who led the study with Professor Bryceson. “There’s a fine balance between effective protection against tumours and infections in the skin and contribution to inflammatory diseases like vitiligo and psoriasis.”

The researchers now aim to harness their findings to optimise the immunotherapy-induced T-cell response to make it even better at eliminating cancer cells in tissues.

Source: Karolinska Institutet

Categories : CancerTags :

Promising Results for Immunotherapy Drug Nivolumab in Advanced Skin Cancer

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Female scientist in laboratory
Photo by Gustavo Fring on Pexels

A phase II clinical trial has demonstrated that patients with advanced cutaneous squamous cell carcinoma can benefit from the immune checkpoint inhibitor nivolumab. The findings were published in the journal CANCER. 

Two other immune checkpoint inhibitors, cemiplimab and pembrolizumab, have been approved by the US Food and Drug Administration for the treatment of advanced cutaneous squamous cell carcinoma in recent years. This new study is the first to report clinical trial results for nivolumab. 

The single-arm trial included 24 patients who received nivolumab at 3mg/kg every two weeks until they experienced cancer progression, developed unacceptable toxicity, or had received 12 months of treatment.  

During the trial, 14 patients (58.3%) benefited from the treatment, with their cancers demonstrating a response. Treatment-related adverse events of any grade occurred in 21 patients (87.5%) and, for and grade ≥ 3, in six patients (25%). One patient discontinued nivolumab due to toxicities. Prior radiotherapy exposure was associated with a worse response. 

“This is the first study to investigate nivolumab in this patient population, and it provides further evidence supporting the use of immune checkpoint blockers as standard therapies in cutaneous squamous cell carcinoma,” said lead author Rodrigo R. Munhoz, MD, of the Hospital Sírio-Libanês, in Brazil. 

An accompanying editorial notes that although the trial was small, its results were similar to those reported with pembrolizumab and cemiplimab. “In addition to providing more assurance to the clinical activity of different [immune checkpoint] inhibitors in this disease, this replicated data may permit a more widespread utilisation of these agents in managing a common disease with global implications,” the authors wrote. 

Source: Wiley

Categories : CancerTags :

Laser Treatments may Prevent Keratinocyte Carcinomas

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Photo by Romina Farias on Unsplash

New research published in Dermatologic Surgery indicates that simple laser treatments to the skin may help to prevent the development of basal cell carcinoma and squamous cell carcinoma, collectively known as keratinocyte carcinoma.

Conducted by a team of researchers from Massachusetts General Hospital, a founding member of Mass General Brigham, the work describes an easy-to-implement strategy to protect skin health.

Nonablative fractional lasers (NAFL) deliver heat in a fractional manner that leaves it fully intact after treatment, unlike ablative fractional lasers that remove the top layer of skin. Currently they are used to treat things such as scars, sun-damaged skin and age spots, but their effectiveness for preventing skin damage is unknown.

To investigate, Mathew Avram, MD, JD, director of the Mass General Dermatology Laser & Cosmetic Center, and his colleagues studied patients who had been successfully treated for facial keratinocyte carcinoma in the past. Such patients have a 35% risk of experiencing a subsequent keratinocyte carcinoma within 3 years and a 50% risk within 5 years.

In the study, 43 patients received NAFL therapy and 52 served as controls and did not receive NAFL therapy.

The rate of subsequent facial keratinocyte carcinoma development over an average follow-up of more than 6 years was 20.9% in NAFL-treated patients and 40.4% in controls, indicating that patients treated with NAFL had about half the risk.

Controlling for age, gender, and skin type, control patients were 2.65-times more likely to develop a new facial keratinocyte carcinoma than NAFL-treated patients.

Also, among patients who developed a facial keratinocyte carcinoma, the time to development was significantly longer in patients treated with NAFL compared with untreated patients.

“These findings suggest that NAFL treatment may have an important role in protecting against subsequent keratinocyte carcinomas,” says Avram.

“While the mechanism of NAFL’s protective effect is not completely understood, it is suspected that NAFL treatment reduces the overall burden of photo damaged keratinocytes and may promote a wound healing response, which gives healthy skin cells a selective advantage.”

Avram noted that additional studies are warranted to more critically assess the role of NAFL in skin cancer prevention, to reveal the duration of its protective effects, and to determine optimal treatment parameters.

“Based on this research, it’s encouraged for patients to have nonablative laser treatments to help prevent skin cancer if they are at risk or notice abnormalities,” says Avram.

Source: Massachusetts General Hospital

Categories : Environmental EffectsTags :

Solar Exposure Guidelines Could be Revised

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Photo by Amy Humphries on Unsplash

Previously published solar exposure guidelines for optimal vitamin D synthesis that were based on a study of skin samples may have to be revised. 

A study published in PNAS has tested the optimum ultraviolet radiation (UVR) wavelengths for human skin production of vitamin D in sunlight.

Though UVR from sunlight can cause sunburn and skin cancer, it is the most important source of vitamin D.

Public health advice on sunshine exposure balances its risk and benefit, which is not a simple task because the health outcomes from UVR exposure vary considerably with wavelength within the sun’s UVR spectrum. For example, the sun’s UVR contains less than 5% short wavelength UVB radiation but this is responsible for over 80% of the sunburn response. Each health outcome from solar exposure has its own unique wavelength dependency.

The link between specific UVB wavelengths and vitamin D production was determined more than thirty years ago in ex vivo skin samples. However, the finding is less well established, with doubts on its accuracy which compromise risk/benefit calculations for optimal solar exposure.

Researchers led by the Professor Antony Young from King’s College London measured blood vitamin D levels in 75 healthy young volunteers, before, during, and after partial or full body exposure to five different artificial UVR sources with different amounts of UVB radiation, to gauge the trade-off between solar exposure benefits, which include vitamin D synthesis, versus the risks of sunburn and skin cancer.

The results were compared against predictions from the old ex vivo vitamin D study, finding that it was not an accurate predictor of benefit from UVR exposure.

The authors’ recommendation is a systematic correction of the ex vivo wavelength dependency for vitamin D. The new study means that many risk benefit calculations for solar UVR exposure must be reviewed with a revised version of the wavelength dependency for vitamin D.

“Our study shows that risk versus benefit calculations from solar exposure may need to be re-evaluated. The results from the study are timely because the global technical committee, Commission internationale de l’éclairage, that sets UVR standards will be able to discuss the findings of this paper to re-evaluate the wavelength dependency of vitamin D. Further research from our group will determine the risk/benefit calculations.”

Professor Antony Young, King’s College London

Source: King’s College London

Categories : New Compounds and TreatmentsTags :

New Molecules Provide Deeper UV Protection

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Two new molecules that release tiny quantities of hydrogen sulfide have been found to prevent skin from ageing after being exposed to ultraviolet light found in sunlight. The study was published in Antioxidant and Redox Signalling.

For the study, the researchers exposed adult human skin cells and the skin of mice to ultraviolet radiation (UVA). UVA causes skin ageing by turning on collagenases, enzymes which eat away at the natural collagen, causing the skin to lose elasticity, sag and wrinkle. UVA also penetrates deeper into skin than the UV radiation that causes sunburns (UVB), and it also damages cellular DNA, leading to mutations that can contribute to some skin cancers. Typical sun creams sit on top of the skin and absorb UV radiation, but they do not penetrate the skin where the long-lasting damage occurs.

For deeper protection, the researchers came up with a new way to protect the deeper layers of skin using two compounds invented at the University of Exeter: AP39 and AP123. The compounds do not protect the skin in the same way traditional sun creams prevent sunburn, but instead penetrate the skin to correct how skin cells’ energy production and usage was turned off by UVA exposure. This then prevented the activation of skin-degrading collagenase enzymes. 

The compounds used in this study were previously shown to have impressive effects in reducing skin inflammation and skin damage after burn injury and atopic dermatitis (eczema). In an anti-ageing context, they prevented human skin cells in test tube experiments from ageing, but this is the first time the effects of photo-ageing have been seen in animals.

The important observation noted was that the compounds only regulated energy production, PGC-1α and Nrf2 in skin that was exposed to UVA. This suggests a novel approach to treating skin that has already been damaged by UV radiation, and could potentially reverse, as well as limit, that damage.

While further research is needed, there could be medical as well as cosmetic implications from this work, where protecting skin from UV light is important. For example, not only premature skin ageing and skin cancers, but UV light allergies, solar urticaria and rare hereditary skin diseases such as xeroderma pigmentosum. The researchers are currently partway through testing newer and more potent molecules able to do the same task using newer approaches.

Source: University of Exeter

Categories : Diet and NutritionTags :

Eating Grapes Protects against Sunburn

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Compounds found in the humble grape may offer a protective effect against the sun’s damaging UV radiation, a new study has found.

Researchers from University of Alabama at Birmingham’s (UAB) Department of Dermatology found that healthy adult participants who ate freeze-dried powdered grapes for 14 days achieved a 74.8% increase in natural skin protection. 

The number of sunburns experienced over a lifetime increases the risk of skin cancer. Sunburns also cause skin damage, which has a cosmetic effect. Sunburns are marked by DNA damage triggering cell apoptosis, as well as the release of inflammatory markers such as prostaglandins, reactive oxygen species, and bradykinin in response to dimers formed by UV radiation. Prostaglandin E2 and histamine levels also rise after a sunburn.
Research in mouse models has shown that polyphenols, found in grapes as well as other fruits and vegetables, can reduce UV radiation damage, as well as reducing the production of inflammatory compounds. As such, this is the first research that shows the consumption of table grapes has a photoprotective effect against the sunburn response in adult humans. The subjects were also given a polyphenol compound, proanthocyanidin, as a topical extract to apply on their skin.

“Study results indicate that oral consumption of grapes has systemic beneficial effects in healthy adults,” said lead author Allen Oak, MD, a dermatologist in the UAB School of Medicine. “These benefits include inhibition of inflammation and repair of DNA damage.”

The preliminary findings also indicated that grapes may help reduce the risk of skin cancer as well, although this requires further research. 
“Grape consumption may act as an ‘edible sunscreen,'” Oak said. “This does not mean that grapes should be used in lieu of sunscreen, but they may offer additional protection which we are eager to continue learning more about. This research is exciting because our current findings provide building blocks for additional studies that may eventuate in an oral photoprotective product from a natural source.”

Source: Medical Xpress

Journal information: Allen S.W. Oak et al. Dietary table grape protects against UV photodamage in humans: 1. clinical evaluation, Journal of the American Academy of Dermatology (2021). DOI: 10.1016/j.jaad.2021.01.035