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Persistent mutations in tumors may predict immunotherapy response: Study - Video

Published On 2023-01-28T09:30:51+05:30  |  Updated On 28 Jan 2023 2:44 PM IST
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Overview

Iinvestigators at the Johns Hopkins Kimmel Cancer Center and its Bloomberg Kimmel Institute for Cancer Immunotherapy have found that a subset of mutations within the overall tumor mutation burden or TMB, termed “persistent mutations,” are less likely to be edited out as cancer evolves, rendering tumors continuously visible to the immune system and predisposing them to respond to immunotherapy.

This persistent mutation load may help clinicians more accurately select patients for clinical trials of novel immunotherapies or predict a patient’s clinical outcome with immune checkpoint blockade - a type of immunotherapy.

The investigators assessed regions of the genome with a single copy per cell and with two copies per cell, and found that the rate of mutation losses was lower in the regions with a single copy than in those with two copies, supporting the idea that mutations in single copy regions would be difficult to eliminate. The distribution of persistent mutations also differed compared to the overall TMB, where a tumor’s TMB was not always concordant with its persistent mutation load. Furthermore, in each tumor type, the team observed differential classification of tumors based on persistent mutations compared to the overall TMB.

The researchers also explored the relationship between persistent mutation load and TMB, using data from seven published cohorts of patients treated with immune-checkpoint blockade therapy across three tumor types: melanoma, nonsmall cell lung cancer and mesothelioma, totaling 485 patients. Again, the team observed that overall TMB and persistent mutation burden were different across the cancers analyzed. There were tumors with a high overall TMB with a smaller subset of persistent mutations, and conversely, there were tumors with a low overall TMB but a higher fraction of persistent mutations.

In further analyses, the scientists evaluated whether a higher persistent mutation load (pTMB) was linked with clinical outcomes among patients with previously untreated tumors from the Cancer Genome Atlas. They found a significant association with prolonged overall survival for lung squamous cell cancer, melanoma and uterine cancer but not for other cancer types studied.

Reference:

Valsamo Anagnostou et al,Nature Medicine,doi 10.1038/s41591-022-02163-w

Speakers

Isra Zaman

B.Sc Life Sciences, M.Sc Biotechnology, B.Ed

Isra Zaman is a Life Science graduate from Daulat Ram College, Delhi University, and a postgraduate in Biotechnology from Amity University. She has a flair for writing, and her roles at Medicaldialogues include that of a Sr. content writer and a medical correspondent. Her news pieces cover recent discoveries and updates from the health and medicine sector. She can be reached at editorial@medicaldialogues.in.

Dr. Kamal Kant Kohli

Dr Kamal Kant Kohli-MBBS, DTCD- a chest specialist with more than 30 years of practice and a flair for writing clinical articles, Dr Kamal Kant Kohli joined Medical Dialogues as a Chief Editor of Medical News. Besides writing articles, as an editor, he proofreads and verifies all the medical content published on Medical Dialogues including those coming from journals, studies,medical conferences,guidelines etc. Email: drkohli@medicaldialogues.in. Contact no. 011-43720751
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