Amazing stuff! Good news! Cancer is history (soon)!
"People who live to 110 years and older have large populations of a rare type of immune cell that can kill cancer.
These killer T cells might help people to live to extraordinarily long ages by fighting off cancer — although this has yet to be proved.
“Most of immune ageing research has focused on decline,” [what a mistake!] ... “Our study suggests that even at extreme old age, the immune system may still selectively adapt.”"
"The current study builds on a 2019 finding by Hashimoto and his colleagues that supercentenarians have relatively large numbers of rare CD4 cytotoxic T lymphocytes (CD4 CTLs).
Cytotoxic cells kill other cells. CD4 CTLs typically make up less than 5% of the total population of T cells in the body. They’re not as well studied as other kinds of T cell, but they are commonly detected during viral infections, and there’s increasing evidence that they can kill cancer cells, including lung cancer and melanoma cells. Hashimoto says that his team wanted to find out at what age CD4 CTLs proliferate.
Supercentenarians are challenging to study because not many people live that long, says Hashimoto. In Japan, where his team did the study, there are only about 150 people aged 110 or older, he says. The study enrolled 28 participants, including some relatively young people: eight individuals aged 70–90, ten centenarians (people 100–109 years old) and ten supercentenarians.
As the researchers had previously found, CD4 CTLs were abundant in supercentenarians. But they were also found in large numbers in people aged 100 and older, suggesting that this immune adaptation begins around that age. The younger people had normal abundance of these cells, with CD4 CTLs making up 4% of their total T cells. The proportion was around 10% in centenarians and around 18% in supercentenarians.
And they found that these cells seem to be responding to specific immune threats. ... In the study’s centenarians and supercentenarians, the researchers found that single clonal lines made up a large percentage of the total CD4 CTLs. In the sample of one centenarian, for example, 53.8% of the cells were identical to each other. This suggests that their immune systems were leaping into action in response to a particular persistent trigger. ...
To get some clues, they examined the receptors found on the most common CD4 killer cell lines. They compared the amino-acid sequences of these cell lines with those in a database of CD4 cell receptors. Around 30 sequences from the study matched those from people with cancer in the database. Matches to people with lung cancer were most frequent, even though none of the people in the study had experienced any kind of cancer during their lives. ..."
From the highlights and abstract:
"Highlights
• CD4 CTLs expand around age 100 without signs of exhaustion
• A CD27−CD28+ state marks the intermediate helper-to-killer transition
• Large private CD4 CTL clones suggest repeated antigen exposure
• Single clones diversify cytokine profiles after ex vivo stimulation
Summary
Our previous study identified CD4 cytotoxic T lymphocytes (CD4 CTLs) as a hallmark of supercentenarians.
CD4 CTLs have primarily been studied in disease contexts; however, their role in healthy aging remains unclear.
Using single-cell immune profiling, we analyzed T cells from supercentenarians and found that CD4 CTLs begin to expand around the age of 100, characterized by sequential CD27/CD28 loss without exhaustion.
CD4 CTLs were dominated by large clones, with top clones averaging 33.3%, indicating repeated stimulation by persistent antigens.
Furthermore, CDR3β sequences of the top clones matched those of T cells expanded in tumors, particularly lung cancer.
Ex vivo stimulation experiments revealed that CD4 CTLs consist of subgroups defined by interleukin expression patterns, suggesting their plasticity within the same clone.
These findings suggest that CD4 CTLs expand and diversify as an adaptation to persistent antigens, potentially contributing to longevity through cancer suppression."
How do people live beyond 110? Abundance of cancer-killing cells might be key "Research on people 110 years and older reveals an immune system that continues to adapt."
Misao Okawa celebrated her 117th birthday in 2015. Is she still alive?
Graphical abstract
Figure 1 Overview of single-cell immune profiling
Figure 6 Characteristics of activated CD4 CTLs
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