Acquired resistance to immune checkpoint therapy is caused by glycoprotein non-metastatic melanoma protein B signal cascade.

ABSTRACT:

Background

Acquired resistance (AR) is a major limitation of immune checkpoint inhibitor (ICI) therapy when treating renal cell carcinoma (RCC). Understanding who will get AR is currently unknown. We hypothesized the T-cell-inhibitory glycoprotein non-metastatic melanoma protein B (GPNMB) to be a prognostic marker for patients with AR.

Methods

Alongside other markers, GPNMB was measured in the blood of RCC patients (n = 39) several times after starting ICI treatment and analyzed for association with Response Evaluation Criteria in Solid Tumors (RECIST) tumor response. To better understand the role of GPNMB in AR, we created an ICI-resistant RenCa mouse kidney cancer model by repeatedly selecting the largest tumors that grew in ICI-treated mice.

Results

Here we show th

SUBMITTER: Chung JS 

PROVIDER: S-EPMC11926377 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature