Deregulation of interferon-gamma receptor 1 expression and its implications for lung adenocarcinoma progression

Figure 1 Canonical signaling pathway of interferon-gamma. The heterotetrameric receptor complex for interferon-gamma (IFN-γ) comprises IFNGR1 and IFNGR2. JAK1 and JAK2 proteins are associated with intracellular domains of IFNGR1 and IFNGR2, respectively. The binding of IFN-γ to its receptor complex promotes the transphosphorylation of JAK1/2, the phosphorylation of IFNGR1, and the recruitment of STAT1, followed by the STAT1 phosphorylation by JAK proteins. Phosphorylated STAT1 translocates into the nucleus to modulate the transcription of genes containing gamma-activated sequence motifs in their promoter regions. IFN-γ: Interferon-gamma; GAS: Gamma-activated sequence; ISGs: Interferon-stiumlated genes.

Figure 2 IFNGR1 and JAK1/2 are downregulated in lung adenocarcinoma. IFNGR1, IFNAR1, JAK1, and JAK2 expression in human lung adenocarcinoma (LUAD) tumors compared to normal tissue tumors. A-D: Selamat Lung dataset; E: The Cancer Genome Atlas from the University of ALabama at Birmingham CANcer data analysis Portal. Expression of IFNGR1 in LUAD based on the patient´s smoking habits. Reformed smoker 1 (< 5 years); Reformed smoker 2 (> 15 years). Results are considered significant (P < 0.05) in all cases, with the exception of IFNAR1 (NS: Not significant).

Figure 3 Interplay between antitumoral and antiviral activities induced by interferon-gamma in the pulmonary context. A: Heat map of interferon-gamma (IFN-γ) signaling components and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) receptor, angiotensin-converting enzyme 2 (ACE2), in lung adenocarcinoma (LUAD). IFNG, IFNGR2, IFNGR1, JAK1, JAK2, and DNAJA3 expression in human LUAD tumors and normal tissue. Selamat Lung datasets; B: Proposed model: There is a functional IFN-γ signaling pathway for controlling cell proliferation and viral infections in normal conditions. In LUAD, there is an increase in the ACE2 expression, facilitating the SARS-CoV-2 infection. Moreover, the expression of IFN-γ signaling components is reduced, decreasing the antiproliferation and antiviral defenses. IFN-γ: Interferon-gamma; GAS: Gamma-activated sequence; ISGs: Interferon-stimulated genes.