A new immune cell model

Researchers from the Francis Crick Institute, the Royal Marsden National Health Service Foundation, and University College London have discovered patterns of immune cells in tumors that can help predict whether kidney cancer patients will respond to immunotherapy
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Clear cell kidney cancer is the most common type of kidney cancer, accounting for approximately 75% of cases
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Treatment usually includes immunotherapy, drugs that help immune cells recognize and attack cancer cells

Their study was published today (October 28) in the journal Cancer Cell .
Scientists analyzed 115 tumor samples from 15 patients with metastatic clear cell renal cell carcinoma who received immunotherapeutic drugs through the ADAPTeR clinical trial.
Nivolumab
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"It is important to analyze multiple samples from each patient, including multiple samples from different parts of the kidney tumor and tumors that have spread to other organs
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As we all know, the molecular information in kidney cancer is distributed in a mosaic pattern in the tumor, so A single sample may not capture all the information that requires a comprehensive analysis," said Lewis Au, who is the co-lead author, oncologist and researcher of the Crick Cancer Kinetics Laboratory

Researchers collect tumor samples at different stages of cancer treatment: before immunotherapy, 9 weeks after treatment begins, when the tumor is removed after surgery, and when treatment stops
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For the three patients, tumor samples were also collected after the death of the patient

In the collected samples, the research team observed different tumor characteristics and immune response measurements to see if there were any corresponding immunotherapy
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This includes the number of different mutations present at the time of tumor diagnosis, and whether specific retroviral components are expressed, that is, the viral DNA present in the human genome

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They found that the increase in the number of specific "cloned" T cell receptors (proteins on the surface of T cells) on the surface of T cells present in the tumor before treatment is related to a greater chance of positive immunotherapy
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If these T cell receptors are maintained during treatment, this is the strongest indicator of treatment effectiveness

Lewis added: "In patients who respond to this immunotherapy, a group of T cells seems to have recognized the tumor through these specific receptors
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These cells with potential tumor-killing activity are located on the tumor, but they need The drug activates it

"Our research also shows that in-depth research on cancer biology in clinical trials can play an incredible role
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The study’s co-author Emine Hatipoglu added: “This study helps us understand why this type of immunotherapy is sometimes effective and sometimes ineffective
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There is a special T cell response that increases the chances of effective treatment

Samra Turajlic, head of the Crick Cancer Dynamics Laboratory, said: "Immunotherapy has changed our ability to treat certain cancers, such as melanoma, skin cancer, kidney cancer, and lung cancer
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But there is still a lot of research that needs to be done to help us.
Learn exactly how it works and why it works for some patients but not others
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Sergio Quezada, Professor of Cancer Immunology and Immunotherapy at the Institute of Cancer Research at University College London, added: “Cancer cells survive and grow because they find a way to avoid the immune system
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Understanding this process will lead to the development of new and more effective Methods to stimulate T cells to fight cancer cells paved the way, which is the key to better treatments
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The patient's perspective

Annie Vigneau-Singh is a kidney cancer patient at the Royal Marsden Hospital.
She has been treated for four years through the ADAPTeR trial since May 2017
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Annie said: "After I was diagnosed in 2015, I had surgery to remove the left kidney, but 6 months later, the scan showed that the cancer was spreading to the lungs
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I can choose to join a new immunotherapy trial called ADAPTeR, and After receiving the drug Nivolumab, Nivolumab could not be used as a treatment option outside of the clinical trials at the time
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Immunotherapy sounds very promising, and I am very eager to try this new therapy
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Within eight weeks of the start of the trial, the scan showed The growth on the lungs has decreased a lot
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I also have no side effects
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Everything is going well and unbelievable
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It is such a positive result and a relief, I can't help crying
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"Unfortunately, the results of the scan in March 2021 showed that my lungs had made slight progress again.
Although I felt good, the drugs were no longer effective for me
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Four years later, I withdrew from the trial and started immediately.
With a new treatment, I hope to participate in another trial in the future
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Although the degree of success in clinical research varies, participation is precisely how cancer treatment progresses
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I am very happy to participate in the ADAPTeR trial and help Royal Mars Den’s oncologist has made new discoveries in the treatment of kidney cancer
.
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The team will continue this work, aiming to learn more about the role of kidney cancer and treatments.
For example, an independent study is currently looking for biomarkers to predict whether an anti-VEGF drug is effective in an individual
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Determinants of anti-PD-1 response and resistance in clear cell renal cell carcinoma