̽��ֱ�� of Cambridge - T-cells

Supertroopers: CAR-T cell cancer therapy

lw355 — Wed, 16 Oct 2024 08:00:15 +0000

A life-saving cancer therapy is being scaled up in Cambridge to deliver more treatments to more patients for more cancers.

Body’s ‘serial killers’ captured on film destroying cancer cells

cjb250 — Tue, 19 May 2015 08:48:01 +0000

In a study published today in the journal Immunity, a collaboration of researchers from the UK and the USA, led by Professor Gillian Griffiths at the ̽��ֱ�� of Cambridge, describe how specialised members of our white blood cells known as cytotoxic T cells destroy tumour cells and virally-infected cells. Using state-of-the-art imaging techniques, the research team, with funding from the Wellcome Trust, has captured the process on film.

“Inside all of us lurks an army of serial killers whose primary function is to kill again and again,” explains Professor Griffiths, Director of the Cambridge Institute for Medical Research. “These cells patrol our bodies, identifying and destroying virally infected and cancer cells and they do so with remarkable precision and efficiency.”

There are billions of T cells within our blood – one teaspoon full of blood alone is believed to have around 5 million T cells, each measuring around 10 micrometres in length, about a tenth the width of a human hair. Each cell is engaged in the ferocious and unrelenting battle to keep us healthy. ̽��ֱ��cells, seen in the video as orange or green amorphous ‘blobs’ move around rapidly, investigating their environment as they travel.

When a cytotoxic T cell finds an infected cell or, in the case of the film, a cancer cell (blue), membrane protrusions rapidly explore the surface of the cell, checking for tell-tale signs that this is an uninvited guest. ̽��ֱ��T cell binds to the cancer cell and injects poisonous proteins known as cytotoxins (red) down special pathways called microtubules to the interface between the T cell and the cancer cell, before puncturing the surface of the cancer cell and delivering its deadly cargo.

“In our bodies, where cells are packed together, it’s essential that the T cell focuses the lethal hit on its target, otherwise it will cause collateral damage to neighbouring, healthy cells,” says Professor Griffiths. “Once the cytotoxins are injected into the cancer cell, its fate is sealed and we can watch as it withers and dies. ̽��ֱ��T cell then moves on, hungry to find another victim.”

̽��ֱ��researchers captured the footage through high-resolution 3D time-lapse multi-colour imaging, making use of both spinning disk confocal microscopy and lattice light sheet microscopy. These techniques involves capturing slices through an object and ‘stitching’ them together to provide the final 3D images across the whole cell. Using these approaches the researchers have managed to elucidate the order the events leading to delivery of the lethal hit from these serial killers.

Reference
Ritter, AT et al. Actin depletion initiates events leading to granule secretion at the immunological synapse. Immunity; 19 May 2015

A dramatic video has captured the behaviour of cytotoxic T cells – the body’s ‘serial killers’ – as they hunt down and eliminate cancer cells before moving on to their next target.

Inside all of us lurks an army of serial killers whose primary function is to kill again and again

Gillian Griffiths

Killer T Cell: ̽��ֱ��Cancer Assassin

Gillian Griffiths/Jonny Settle

Killer T-Cell

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Immune cells found near tumours boost breast cancer survival

fpjl2 — Tue, 10 Jun 2014 09:36:41 +0000

̽��ֱ��researchers looked for an immune cell called a killer T cell which specialises in destroying rogue cells in the body, such as cancer cells.

̽��ֱ��Cancer Research UK study found that when these immune cells were present, survival improved for women with ER-negative and ER-positive HER2-postive breast cancer. However, survival didn’t change for women with ER-positive HER2-negative breast cancer.

Study author, Dr Raza Ali, National Institute for Health Research clinical lecturer at the Cancer Research UK Cambridge Institute, ̽��ֱ�� of Cambridge, said: “Cancer often finds ways to escape the immune system, but helping immune cells to recognise cancer as a threat - and attack it - provides a promising and powerful avenue for new treatments. We’ve shown that women who have killer T cells present at the site of their tumour are likely to live longer.

“This important insight could help doctors personalise a woman’s treatment based on her immunological profile and also suggests that new treatments should harness the immune system to fight cancer.”

Immune cells were counted and analysed from samples collected from 12,439 breast cancer patients from four different studies across England and Canada*.

̽��ֱ��research, published today in the journal Annals of Oncology, shows that infiltration into the tumour by killer T cells flags up how certain patients should be treated. ̽��ֱ��finding also suggests that chemotherapy could be given alongside immunotherapy drugs. Chemotherapy treatment such as doxorubicin in particular may be enhanced when killer T cells are present.

Professor Carlos Caldas, senior group leader at the Cancer Research UK Cambridge Institute, ̽��ֱ�� of Cambridge, said: “ ̽��ֱ��more we learn about how precisely the immune system interacts with breast cancer the better we are able to fine tune the treatments we give to patients - and the sooner we can save more lives.

“This was the largest ever study of its type looking at data from over 12,000 patients. Crucial research such as this is only possible due to the collaboration available at the Cambridge Cancer Centre, a partnership between Cancer Research UK, the ̽��ֱ�� of Cambridge and Addenbrooke’s Hospital.”

Professor Peter Johnson, Cancer Research UK’s chief clinician, said: “This research highlights the great strides we are making in understanding the complex interplay between cancer and the body’s immune system. These studies are key to informing how we are best able to treat patients in the clinic and to design better drugs that make the best use of the body’s own defences.”

Women with breast cancer are 10 per cent more likely to survive for five years or more if they have certain immune cells near their tumour, according to new research.

̽��ֱ��more we learn about how precisely the immune system interacts with breast cancer the better we are able to fine tune the treatments

Carlos Caldas

Alex Ritter/Gillian Griffiths

Killer T-cell

**Data were collected from three different observational studies including from East Anglia, Nottingham and British Columbia Canada as well as a randomised control trial known as the NEAT trial.

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New target to fight HIV infection identified

gm349 — Tue, 01 Oct 2013 09:14:47 +0000

A mutant of an immune cell protein called ADAP (adhesion and degranulation-promoting adaptor protein) is able to block infection by HIV-1 (human immunodeficiency virus 1), new ̽��ֱ�� of Cambridge research reveals. ̽��ֱ��researchers, who were funded by the Wellcome Trust, believe that their discovery will lead to new ways of combating HIV.

Professor Chris Rudd from the Department of Pathology, who led the research, said: “One exciting aspect about this new target for HIV intervention is that we should be able to fight HIV without compromising the immune system’s ability to battle infections.”

HIV infections cause a severe and selective depletion of T-cells, a type of white blood cell that plays a major role in the immune system. Infections result when the HIV virus enters T-cells of the immune system by binding to the surface receptor CD4. Once it enters the cell, it replicates or reproduces itself rapidly, and then spreads to other T-cells by releasing the virus. This spread can occur between an infected T-cell and an uninfected attached T-cell. ̽��ֱ��researchers found that an ADAP mutant is able to interfere with HIV-1 infection by targeting two events, by reducing the replication of the virus, and the contact between infected and uninfected T-cells.

Professor Rudd added: “ ̽��ֱ��ADAP mutant is potent in its interference of HIV-1 transmission because it targets simultaneously two critical events, viral replication and the spread of the virus from one T-cell to another. One therapeutic possibility is the reconstitution of infected individuals with T-cells expressing the mutant that are relatively resistant to HIV infection and which can react against the virus.”

According the World Health Organisation, there are currently 35.3 million people living with HIV. Although the number of new HIV infections has dropped, it remains a major global public health issue. In the past three decades, it has killed more than 25 million people.

Scientists find mutant protein blocks HIV infection and transmission.

One exciting aspect about this new target for HIV intervention is that we should be able to fight HIV without compromising the immune system’s ability to battle infections.

Professor Chris Rudd

NIAID

HIV-infected H9 T-cell

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