In our observation, there are two plausible explanations for the limited efficacy of immunotherapy: First, we found a high proportion of CD8+ Tdys in NSCLC patients, which was even worse in patients with LNM; Second, some immunoregulatory barriers, such as CMVs and CAFs, were associated with poor infiltration and dysfunction of CD8+ T cells. The gene discussed is CD8A; the disease is non-small cell lung carcinoma.