Background: Immunotherapy has had a high success rate in treating lung adenocarcinoma (LUAD) for several decades. However, many patients do not benefit from immunotherapy alone. Recent studies revealed that a combination of immunotherapy and radiotherapy (RT) stimulates a good systemic immune response to LUAD. However, clinical and experimental evidence suggest that RT may give rise to primary immunodeficiency, facilitating tumor immunity escape. Little is known about the molecular mechanisms whereby RT and stereotactic body radiotherapy (SBRT) influence tumor immunogenicity and the effectiveness of immunotherapy in patients with LUAD.Methods: We investigated molecular markers that predict response to combination of immunotherapy and SBRT in the treatment of LUAD using bioinformatics.Results: SBRT significantly upregulated the expression of PTPRC, LILRB2, TLR8, CCR5, and PLEK and significantly downregulated the expression of CXCL13, CD19, and LTA. Among these genes, the expression of PTPRC, TLR8, and CCR5 was associated with responsiveness to immunotherapy after SBRT. However, only TLR8 and CCR5 expression were associated with an improved prognosis. Further analysis revealed that TLR8 and CCR5 expression increased responsiveness to immunotherapy by promoting M0 macrophage and memory B cell infiltration of LUAD tissues.Conclusions: In patients with LUAD, TLR8 and CCR5 expression are potential markers of a favorable response to combined immunotherapy and RT.