OX40 and LAG3 are associated with better prognosis in advanced gastric cancer patients treated with anti-programmed death-1 antibody

Abstract

Background Anti-PD-1 monoclonal antibody, nivolumab, has shown efficacy for advanced gastric cancer (AGC). However, the specific immune cell subsets predominantly activated during the period of anti-PD-1 therapy for AGC have not been clarified. Methods Peripheral blood of 30 AGC patients treated with nivolumab was prospectively obtained before the initial and second administrations and at the time of progressive disease (PD). The proportions of immune cell subsets and the serum concentrations of cytokines were systematically analysed by flow cytometry. Associations of subsets and serum cytokines with therapeutic effects were evaluated. Results After the initial administration, significant increases in activated central/effector memory, activated effector T cells, and activated T-helper 1 subsets were observed. At the time of PD, activated regulatory T cells, LAG3-positive CD4+/CD8+ T cells, and TIM3-positive CD4+/CD8+ T cells increased significantly. Significant positive correlations were shown between progression-free survival and proportions of LAG3-positive CD4+/CD8+ T cells and of OX40-positive CD4+/CD8+ T cells (log-rank p = 0.0008, 0.0003, 0.0035 and 0.0040). Conclusions Nivolumab therapy enhances activation of central/effector memory and effector subsets of CD4+/CD8+ T cells. The expression levels of LAG-3 and OX40 on T cells correlated with the efficacy of nivolumab therapy and could be reasonable biomarkers for anti-PD-1 therapy.

Single-cell RNA landscape of intratumoral heterogeneity and immunosuppressive microenvironment in advanced osteosarcoma

“…7d ). Importantly, we also found that these cells positively expressed the T cell exhaustion inhibitory receptors including TIGIT and LAG3 56 , 57 (Fig. 7d ), suggesting that the CD8 + T cells become exhausted after the initial activation phase in OS.…”

Predictive impact of C-reactive protein to albumin ratio for recurrent or metastatic head and neck squamous cell carcinoma receiving nivolumab

“…Recently, the correlation between the baseline IL-6 and CRP in melanoma treated with immune checkpoint inhibitors (ICIs) or chemotherapy was demonstrated, and higher levels of IL-6 were significantly associated with poor survival 37 . On the other hand, no significant change of systemic levels of IL-6 during ICI treatment has been observed in the studies of melanoma 38 and gastric cancer 39 . In addition, several reports have already shown that CAR is an important prognostic factor for SCC treated with chemoradiotherapy 24 or cytotoxic agents 26 .…”

The Next-Generation Immune Checkpoint LAG-3 and Its Therapeutic Potential in Oncology: Third Time’s a Charm

“…Paradoxically, some clinical reports indicated a favorable outcome of cancer patients when LAG-3 expression is observed on tumor-infiltrating immune cells. This is the case for breast cancer [ 80 , 81 ], esophageal adenocarcinoma [ 82 ], and advanced gastric cancer patients treated with PD-1 blocking mAbs [ 83 ]. Here, LAG-3 expression could be considered a marker for T-cell activation.…”