Photo Credit: Burcu Onter

The following is a summary of “Changes in circulating immune biomarkers following nivolumab with or without ipilimumab for metastatic anal cancer (NCI9673),” published in the January 2024 issue of Oncology by Morris, et al.

For an NCI9673 phase II trial, researchers sought to assess the progression-free survival (PFS) of nivolumab (N) with or without ipilimumab (I) in metastatic squamous cell carcinoma of the anal canal (SCCA). The analysis focused on immune biomarkers to better understand the impact of these treatments on immune cell populations.

Peripheral blood mononuclear cells (PBMCs) were collected from 47 patients (24 on N and 23 on N+I) at pretreatment, week 9, and progression. Immune cell populations, including effector CD4 T cells, CD8 T cells, natural killer (NK) cells, and regulatory T cells, were assessed for expression of immune inhibitory (PD-1, CTLA-4, TIM-3, LAG-3, TIGIT) and stimulatory (OX40, ICOS) markers using flow cytometry. Comparisons between N and N+I arms were made, and changes in biomarker expression were analyzed.

At baseline, TIGIT expression was significantly higher on CD4 and CD8 T cells than other checkpoint biomarkers (P < 0.0001). In the N+I arm, CD4 T cells exhibited increased TIGIT expression at progression compared to N alone (21.3% vs. 10.9%, P = 0.08). NK cells in the N arm showed decreased TIGIT expression at progression relative to baseline (14.1% vs. 5.9%, P = 0.06). Responders to N demonstrated increased OX40 expression on CD4 T cells but decreased expression on NK cells at week 9 relative to baseline compared to non-responders.

The immune biomarker analysis suggested that TIGIT may play a crucial role in the treatment effect of nivolumab and nivolumab plus ipilimumab in metastatic SCCA. The distinct modulation of TIGIT expression on various immune cell populations emphasized its potential as a novel therapeutic target for metastatic SCCA treatment.

Reference: ascopubs.org/doi/10.1200/JCO.2024.42.3_suppl.3