A Search for Novel Cancer/Testis Antigens in Lung Cancer Identifies VCX/Y Genes, Expanding the Repertoire of Potential Immunotherapeutic Targets

Abstract

Cancer/testis (CT) antigens are potential immunotherapeutic targets in cancer. However, the expression of particular antigens is limited to a subset of tumors of a given type. Thus, there is a need to identify antigens with complementary expression patterns for effective therapeutic intervention. In this study, we searched for genes that were distinctly expressed at a higher level in lung tumor tissue and the testes compared to other non-tumor tissues and identified members of the VCX/Y gene family as novel CT antigens. VCX3A, a member of the VCX/Y gene family, was expressed at the protein level in approximately 20% of lung adenocarcinomas and 35% of squamous cell carcinomas, but not expressed in normal lung tissues. Among CT antigens with concordant mRNA and protein expression levels, four CT antigens, XAGE1, VCX, IL13RA2, and SYCE1, were expressed, alone or in combination, in about 80% of lung adenocarcinoma tumors. The CT antigen VCX/Y gene family broadens the spectrum of CT antigens expressed in lung adenocarcinomas for clinical applications.

Profiling cancer testis antigens in non–small-cell lung cancer

“…In our analysis, TGIF2LX was expressed in both histological subtypes of NSCLC and showed dominant nuclear staining in 5.7% of NSCLC cases. Variable charge X-linked protein 1 (VCX) is involved in spermatogenesis and has recently been suggested to be a CTA in NSCLC (33). We confirmed nuclear staining in the IHC analysis in 62.9% of NSCLC cases.…”

Immunoproteasome deficiency is a feature of non-small cell lung cancer with a mesenchymal phenotype and is associated with a poor outcome

“…Immunohistochemistry was performed using a Leica Bond Max automated stainer (Leica Biosystems) (4,48). The validated primary antibodies used were PSMB8 (LMP7, 1:200, mouse monoclonal; Abcam ab58094), CDH1 (prediluted, mouse monoclonal clone NCH-38; Dako ISO59), and CDH2 (1:50, rabbit monoclonal clone D4R1H; Cell Signaling Technology 13116).…”

“…Expression levels of 49 genes representing proteasome and immunoproteasome subunits across 42 NSCLC cell lines encompassing the heterogeneity of known driver mutations (SI Appendix, Section 1) were derived from global gene expression profiles (4,5) [Gene Expression Omnibus (GEO) accession no. GSE32863] and subjected to unsupervised clustering analysis.…”

Effect of chromium disilicide and titanium nitride nanoparticles on the expression of NAMPT, E2F8, FAS, TBX3, IL13RA2, and UPS7 genes in mouse liver

“…Interleukin 13 receptor, α2 (IL13RA2) has high affinity to interleukin-13 and highly expressed in colorectal cancer, glioblastoma and other malignant tumors, is associated with invasion and liver metastasis [15,16]. Moreover, low-dose cadmium has growth-promoting effects on NPrEC cells and induces transient overexpression of genes with oncogenic and immunomodulation functions, including TNF and Il13ra2 [17]. Ubiquitin specific peptidase 7 (USP7), also known as herpes virus-associated ubiquitin-specific protease (HAUSP), is hydrolase that deubiquitinates target proteins such as FOXO4, p53/TP53, MDM2, PTEN, PPARG, and other and thus participate in control of cell growth repression and apoptosis [18][19][20].…”