The tumor microenvironment plays a vital role in tumor progression and treatment response. However, the association between immune cell concentrations in primary tumor and blood indexes remains unknown. Thus, we enrolled patients with gastric cancer (GC) in two cohorts. We used multiplexed immunohistochemistry to quantify in situ proteins covering rare cell types at sub-cellular resolution in 80 patients with GC in the first cohort. A high correlation between the LMR (lymphocyte-to-monocyte ratio)/NLR (neutrophil-to-lymphocyte ratio) and tumor immune microenvironment was found. The density of exhausted CD8 T cells including CD8⁺PD1⁻TIM3⁺, CD8⁺LAG3⁺PD1⁺, CD8⁺LAG3⁺PD1⁻, CD8⁺LAG3⁺PD1⁺TIM3⁻ was negatively associated with LMR and positively associated with NLR (p < 0.05). Additionally, the higher density of macrophages in tumor core was associated with a higher platelet-to-lymphocyte ratio and systemic immune-inflammation index. Furthermore, we validated the prognostic value of LMR and NLR in an independent cohort of 357 gastric cancer patients receiving immunotherapy. Higher LMR at baseline was significantly associated with superior immune-related PFS (irPFS) and a trend of superior immune-related OS (irOS). Higher NLR was associated with inferior irOS. In conclusion, blood indexes were associated with immune cells infiltrating in primary tumors of GC. NLR and LMR are associated with the density of exhausted CD8⁺ T immune cells, which leads to prognostic values of immunotherapy.

Background: Narcolepsy type 1 (NT1) is primarily caused by a malfunctioning immune system in which T-cells damage the hypothalamus. To elucidate the causal relationships between biomarkers in T-cells and NT1, we employed Mendelian randomization (MR) analysis.Methods: We conducted a two-sample MR analysis utilizing genetically predicted T-cell traits to examine their effects on NT1. Genome-wide association study summary data were extracted from studies by Valeria (3,757 participants) for 211 T-cell traits, Ollila (6,073 cases and 84,856 controls) for NT1. The MR analysis was executed at two threshold levels. Inverse variance weighted, Wald ratio, weighted median, and MR-Egger regression methods were used for the MR analysis. Odds ratios (ORs) were calculated, and heterogeneity tests, as well as pleiotropy tests, were conducted.Results: After Bonferroni correction at the significant level (p < 1.18 × 10⁻⁴), a higher ratio of naive CD4⁻ CD8⁻ T-cells was identified as a risk factor for NT1 (OR = 10.50; 95% CI: 6.98, 15.90, p = 3.89 ×10⁻²⁹). Conversely, CD4 on HLA DR⁺ CD4⁺ T cells (mean fluorescence intensity, MFI) exhibited a negative correlation with NT1. At nominally significant levels (p < 0.05) for both threshold levels, HVEM (herpesvirus entry mediator) on naive CD8⁺ T cells (MFI) was suggested as a protective factor for NT1. Additionally, a higher ratio of CD25⁺⁺ CD45RA⁻ CD4 not regulatory T cells, CD127 on CD45RA⁻ CD4 not regulatory T cells (MFI), CD127 on CD28⁺ CD4⁺ T cells (MFI), CD3 on HLA DR⁺ T cells (MFI), and CD3 on HLA DR⁺ CD4⁺ T cells (MFI) were suggested as risk factors for NT1.Conclusion: This study confirmed the causal effects of CD4⁺ and CD8⁺ T-cells on NT1 and found several novel T-cell-related characteristics.