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Tumor Immunotherapy01:27

Tumor Immunotherapy

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Immunotherapy is a treatment that boosts or manipulates the immune system to fight diseases, including cancer. For instance, by stimulating an immune response through vaccinations against viruses that cause cancers, like hepatitis B virus and human papillomavirus, these diseases can be prevented. Nonetheless, some cancer cells can avoid the immune system due to their rapid mutation and division. The immune response to many cancers involves three phases: elimination, equilibrium, and escape.
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Cancer-Critical Genes II: Tumor Suppressor Genes01:05

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Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
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  1. Home
  3. Blood-based Tumor Mutational Burden Impacts Clinical Outcomes Of Immune Checkpoint Inhibitor Treated Breast And Prostate Cancers.
  1. Home
  3. Blood-based Tumor Mutational Burden Impacts Clinical Outcomes Of Immune Checkpoint Inhibitor Treated Breast And Prostate Cancers.

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Blood-based tumor mutational burden impacts clinical outcomes of immune checkpoint inhibitor treated breast and

Reagan M Barnett1, Albert Jang2,3, Sree Lanka3

  • 1Guardant Health, Inc, Palo Alto, California, USA.

Communications Medicine
|December 2, 2024

View abstract on PubMed

Summary
This summary is machine-generated.

Blood-based tumor mutation burden (bTMB) is not a reliable predictor of immune checkpoint inhibitor (ICI) response in advanced breast and prostate cancers. This study found bTMB did not independently benefit patients with refractory disease.

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Area of Science:

  • Oncology
  • Genomics
  • Immunotherapy

Background:

  • Breast and prostate tumors often show limited response to immune checkpoint inhibitors (ICIs).
  • Tissue-based tumor mutation burden (tTMB) is a known predictive biomarker for ICI response, even in 'cold tumors'.
  • Blood-based tumor mutation burden (bTMB) serves as an alternative biomarker when tTMB is unavailable.

Purpose of the Study:

  • To evaluate the predictive value of blood-based tumor mutation burden (bTMB) for immune checkpoint inhibitor (ICI) response in metastatic breast and prostate cancers.
  • To investigate the association between bTMB and genomic alterations in a large database.

Main Methods:

  • Retrospective analysis of metastatic breast and prostate cancer patients treated with ICIs after liquid biopsy.
  • Assessment of multiple bTMB-High cut-offs and their correlation with clinical outcomes.
  • Querying the Guardant Health genomic database (N=13,992) for bTMB and genomic alteration associations.

    • Main Results:

    • In a clinical cohort (N=48), ICI treatment was common after multiple prior therapies, with a median bTMB of 16.4 mut/Mb.
    • The overall response rate was 16.7%, with limited benefit observed in patients with bTMB <16 mut/Mb.
    • High bMSI correlated with higher bTMB (r=0.66, p=0.000), and common genomic alterations in bTMB-high patients included TP53, PIK3CA, and BRCA2.

    Conclusions:

    • The use of bTMB to guide ICI treatment decisions in refractory advanced breast and prostate cancers was infrequent.
    • bTMB did not independently predict ICI benefit in this patient population.
    • Further research is needed to identify robust biomarkers for ICI response in these cancers.