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Immunotherapy and Tumor mutational burden (TMB): A Dynamic Duo

NextEdge Admin

04 May 2024

3 min 4 sec

Tumor mutational burden (TMB) serves as a pivotal biomarker in oncology, revealing the frequency of somatic mutations within a tumor’s genome. Elevated TMB levels signify a tumor’s heightened genetic instability and propensity for rapid mutation accumulation, which in turn fosters increased neoantigen expression. These neoantigens serve as beacons for the immune system, facilitating tumor recognition and subsequent immune response.

Across various cancer types, including colorectal cancer, melanoma, and non-small cell lung cancer (NSCLC), high TMB has emerged as a promising indicator of potential responsiveness to immunotherapy. Immunotherapeutic agents like pembrolizumab, nivolumab, and ipilimumab have shown efficacy in patients with high TMB, even in cases where tumors exhibit microsatellite stability (MSS).

The clinical significance of TMB extends beyond its prognostic value, serving as a predictive marker for treatment outcomes. Patients with high TMB often experience improved response rates and prolonged progression-free survival when treated with immune checkpoint inhibitors (ICIs). This expanded applicability of immunotherapy beyond conventional PD-L1 testing broadens the pool of patients who may benefit from these therapies.

Next-generation sequencing (NGS) has revolutionized TMB assessment, enabling comprehensive analysis through targeted gene panels or whole exome sequencing. Moreover, ongoing research explores the feasibility of assessing TMB through blood samples, leveraging circulating tumor DNA (ctDNA) analysis. While still primarily utilized within research settings, blood-based TMB testing holds promise for future clinical applications.

The decision to undergo TMB testing should be made in consultation with healthcare professionals, considering individualized factors and tumor characteristics. For patients with MSS tumors, TMB evaluation can inform treatment strategies, potentially identifying candidates for immunotherapy regimens tailored to their tumor’s genetic profile.

TMB serves as a cornerstone biomarker in modern oncology, providing valuable insights into tumor biology and guiding personalized treatment approaches. Its integration into clinical practice heralds a new era of precision medicine, offering hope for improved outcomes and therapeutic efficacy in diverse cancer populations.