Nat Med Clinical Breakthrough: High IL-8 Levels in Blood and Tumors Linked to Reduced Efficacy of PD-L1 Inhibitors

May 14, 2020 /Bio ValleyBIOON /--Although elevated plasma interleukin-8 (pIL-8) levels are associated with poor outcomes in immune checkpoint blockade, this has not been comprehensively evaluated in large randomized studies.

Recently, researchers from Genentech published a study titled "High systemic and tumor-associated IL-8 correlates with reduced clinical benefit of PD-L1 blockade" in Nature Medicine, analyzing peripheral blood mononuclear cells from 1,445 patients with metastatic urothelial carcinoma (mUC) and metastatic renal cell carcinoma treated with the PD-L1 monoclonal antibody atezolizumab (Tecentriq).TumorExpression of pIL-8 and IL-8 gene in the middle cycle.

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Researchers found that high levels of IL-8 in plasma, peripheral blood mononuclear cells, and tumors were associated with reduced efficacy of atezolizumab in patients with metastatic urothelial carcinoma (mUC) and metastatic renal cell carcinoma, even in the presence of typical CD8+ T cell–inflamedTumorThis was also observed in the Chinese population. Furthermore, low baseline pIL-8 levels were associated with increased response to atezolizumab and chemotherapy in patients with mUC.

Researchers also found that in patients with metastatic urothelial carcinoma (mUC) who had received prior treatment, a reduction in plasma IL-8 (pIL-8) levels was associated with improved overall survival when treated with atezolizumab without chemotherapy. Single-cell RNA sequencing of immune cells revealed that IL-8 is primarily expressed in circulating and intratumoral myeloid cells, and high IL-8 expression is associated with downregulation of antigen presentation mechanisms.

Therefore, researchers believe that therapies capable of reversing IL-8-mediated bone marrow inflammation are crucial for improving the prognosis of patients receiving immune checkpoint inhibitor therapy. (Bioon.com)