J Immunother Cancer: Obesity weakens the effectiveness of anti-PD-1 immunotherapy in patients with kidney cancer

Obesity is a major risk factor for kidney cancer, but we still don't fully understand its effects on anti-tumor immunity and immunotherapy outcomes.
In view of the increasing number of immuno-checkpoint inhibitors that will be used to treat metastases, and the growing evidence that there is an obesity paradox in the context of cancer immunotherapy (the prognostication of obese cancer patients is relatively good), it is important to decipher these associations."
study looked at the relationship between host obesity and prognosis for treatment based on anti-programmed cell death proteins (PD-1) in patients with renal cell carcinoma (RCC) and in mouse models of renal tumors.
followed 73 patients with advanced kidney cancer treated with standard anti-PD-1 for more than six months and calculated total survival (OS) and progress-free survival (PFS).
In addition, the researchers collected tumor tissue from 19 patients with primary kidney tumors, divided into obesity (BMI≥30 kg/m) and non-obesity (BMI≥30 kg/m) groups by body mass index (BMI), and used a flow cytometer to detect the proportion and esophology of CD8 plus T cells in tumor tissue, including PD-1 status.
mice were treated with combined anti-PD-1 to assess anti-tumor immunity.
obesity was associated with a decrease in the frequency of PD-1hiCD8 plus TILs in activated primary patients, and in obese patients, patients with kidney cancer treated with anti-PD-1 showed shorter PFS (p-0.0448) and OS (p-0.0288).
the frequency of immersive PD-1high CD8 plus T cells in tumor tissue in patients with primary kidney cancer was reduced, and the results were validated in mouse models.
After anti-PD-1 immunotherapy, the survival rate of kidney tumor mice with different treatment methods was different for both thin mice and obese mice, while obesity decreased the proportion of patients treated (73% of thin mice vs. 44% of obese mice).
thin and obese tumors in mice with responses showed similar immunogenetic characteristics, mainly PD-1int interferon (IFN) γ-CD8-T cell immersion, decreased inhibitory cells (MDSC) from myelin sources, and obtained a more favorable ratio of CD44-CD8-T-cells and MDSC.
lecytosin (IL)-1 beta in obese mice increased the therapeutic response rate to 58% and reduced the build-up of MDS in tumors.
, the study showed that obesity was associated with a decrease in the effectiveness of anti-PD-1 treatment for kidney cancer, in part because of elevated levels of inflammatory IL-1 beta, highlighting the need to continue research on this critical issue.