Combinatorial Biomarkers

Combinatorial Biomarkers in Immune Checkpoint Therapy

Immune checkpoint treatment (ICT) involves preventing T lymphocytes from detecting and attacking cancer cells by inhibiting inhibitory checkpoint molecules. These therapies can improve patient outcomes by enhancing the anti-tumor immune response.

Biomarkers are measurable traits that can indicate whether a disease exists or is progressing. Combinatorial biomarkers refer to the use of multiple biomarkers in combination to provide a more comprehensive picture of a patient's disease. This approach may increase the sensitivity and specificity of biomarker-based diagnostics and treatment monitoring.

Advantages of Combinatorial Biomarkers

• Better predictive capacity
  Combinatorial biomarkers reflect both the tumor mutational status and immune response biomarkers, consider the dynamic and complex interactions of tumors and the host immune system, and enable integration between cancer cell biology and immune cell responses which improves the predictive capability of the biomarker.
• More tailored and precise approach to cancer therapy
  Combining immune checkpoint therapy with combinatorial biomarkers may allow for the reliable prediction of response to immune checkpoint therapy into different kinds of tumors, allowing clinicians to better select patients for immune checkpoint therapy, tailor treatment strategies to individual patients, and potentially improve treatment outcomes.

Clinical Research of Combinatorial Biomarkers

A retrospective investigation discovered genetic mutations in tumor cells of the AT-rich interactive domain-containing protein 1A (ARID1A) and production of the immune cytokine CXCL13 in pre-treatment tumor samples as predictive biomarkers for ICT. The combination of the two biomarkers in baseline tumor tissues enhanced overall survival (OS) and predictive capacity when compared to either biomarker alone. The combination of CXCL13 and the ARID1A mutation may improve patient selection for immune checkpoint therapy in metastatic urothelial carcinoma (mUCC).

Fig 1 The combination of ARID1A mutation and baseline CXCL13 expression increased predictiveness over single biomarkers.¹

Tumor mutational burden (TMB) combined with a T cell-inflamed gene-expression profile or TMB combined with PD-L1 expression improved prediction ability when compared to single biomarkers. Recent research of over 1,000 ICT-treated patients with seven different forms of cancer found that a multivariable predictor of response surpassed TMB alone.

The combination of CD276 and T-cell immunoglobulin domain and mucin domain 3 (TIM-3) is an excellent predictive biomarker panel. The combination of CD276 and TIM3 is found to be linked with urothelial carcinoma (UC) patient survival. Indicators of CD276-TIM3 function as independent prognostic biomarkers to predict UC outcome regardless of tumor stage or grade.

Fig 2 CD276 and TIM-3 in combination is an independently poor prognostic biomarker of UC.²

In conclusion, the combination of immune checkpoint therapy with combinatorial biomarkers represents a promising approach to cancer treatment. This technique has the potential to improve immunotherapy accuracy and effectiveness while also improving patient outcomes. Creative Biolabs provides professional biomarker joint services to improve the effect of your ICT and optimize the selection of biomarkers. In the event that you require further information, please do not hesitate to contact us.

References

1. Goswami, Sangeeta et al. "ARID1A mutation plus CXCL13 expression act as combinatorial biomarkers to predict responses to immune checkpoint therapy in mUCC." Science translational medicine vol. 12,548 (2020): eabc4220.
2. Tsai, Chung-Ying et al. "Combination Biomarker of Immune Checkpoints Predict Prognosis of Urothelial Carcinoma." Biomedicines vol. 10,1 8. 22 Dec. 2021.

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