Kidney Cancer Treatments and Tumor Biology Activate Different Immune-Modifying Processes in Patients

Immunotherapy and anti-angiogenic treatment combination shows unique immunomodulation, highlighting tumor biology's role in interactions of infiltrating immune cells in treatment responses.
Clinical trial comparing two therapies for advanced renal cell carcinoma shows that different immunomodulatory mechanisms are at work depending on the type of treatment and the genetic make up of the cancer. (Representational Image: Wikimedia Commons)
Clinical trial comparing two therapies for advanced renal cell carcinoma shows that different immunomodulatory mechanisms are at work depending on the type of treatment and the genetic make up of the cancer. (Representational Image: Wikimedia Commons)

A research article, published online in Cancer Discovery on February 22, 2024 about a clinical trial comparing two therapies for advanced renal cell carcinoma shows that different immunomodulatory mechanisms are at work depending on the type of treatment and the genetic make up of the cancer. 

The trial was conducted by a group of researchers at different study centers with Toni Choueiri, MD, Director, The Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, as a co-first author of the study.

The phase III trial, dubbed JAVELIN Renal 101, demonstrated that patients treated with avelumab, a type of immunotherapy, and axitinib (an anti-angiogenic) had longer progression-free survival (PFS) than those treated with sunitinib. 

The molecular make-up of the tumor, as well as the treatment administered to patients, affects the variety and activity of immune cells mobilized in response to treatment. (Representational Image: Wikimedia Commons)
The molecular make-up of the tumor, as well as the treatment administered to patients, affects the variety and activity of immune cells mobilized in response to treatment. (Representational Image: Wikimedia Commons)
In analyzing participants' blood and tumor samples, researchers found that treatment with avelumab and axitinib led to a greater change in T-cell repertoire but less change in overall T-cell numbers than treatment with sunitinib. 

Patients in the avelumab and axitinib cohort whose tumors had mutations in two or more of 10 genes previously linked to PFS had distinct profiles of circulating and tumor-infiltration immune cells, compared to those with wild-type or single-mutant tumors. 

The molecular make-up of the tumor, as well as the treatment administered, affects the variety and activity of immune cells mobilized in response to treatment.

Clinical trial comparing two therapies for advanced renal cell carcinoma shows that different immunomodulatory mechanisms are at work depending on the type of treatment and the genetic make up of the cancer. (Representational Image: Wikimedia Commons)
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The findings highlight that the mechanisms of immune modulation are different in patients treated with immunotherapy and anti-angiogenic combinations. The results also point to the role of tumor biology in the diversity and actions of tumor-infiltrating immune cells brought into action by these treatments.

The findings might be important for predicting or understanding treatment outcomes in advanced kidney cancer.

The trial was sponsored by Pfizer and conducted under an alliance between the healthcare business of Merck KgaA, Darmstadt, Germany, and Pfizer.

(NJ/Newswise)

Clinical trial comparing two therapies for advanced renal cell carcinoma shows that different immunomodulatory mechanisms are at work depending on the type of treatment and the genetic make up of the cancer. (Representational Image: Wikimedia Commons)
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