Expression of cancer–testis antigens in the immune microenvironment of non‐small cell lung cancer

Abstract

The antigenic repertoire of tumors is critical for successful anti‐cancer immune response and the efficacy of immunotherapy. Cancer–testis antigens (CTAs) are targets of humoral and cellular immune reactions. We aimed to characterize CTA expression in non‐small cell lung cancer (NSCLC) in the context of the immune microenvironment. Of 90 CTAs validated by RNA sequencing, eight CTAs (DPEP3, EZHIP, MAGEA4, MAGEB2, MAGEC2, PAGE1, PRAME, and TKTL1) were selected for immunohistochemical profiling in cancer tissues from 328 NSCLC patients. CTA expression was compared with immune cell densities in the tumor environment and with genomic, transcriptomic, and clinical data. Most NSCLC cases (79%) expressed at least one of the analyzed CTAs, and CTA protein expression correlated generally with RNA expression. CTA profiles were associated with immune profiles: high MAGEA4 expression was related to M2 macrophages (CD163) and regulatory T cells (FOXP3), low MAGEA4 was associated with T cells (CD3), and high EZHIP was associated with plasma cell infiltration (adj. P‐value < 0.05). None of the CTAs correlated with clinical outcomes. The current study provides a comprehensive evaluation of CTAs and suggests that their association with immune cells may indicate in situ immunogenic effects. The findings support the rationale to harness CTAs as targets for immunotherapy.

Can Tumour Antigens Act as Biomarkers for the Early Detection of Non-Small Cell Lung Cancer?

“…Breast and prostate cancers are examples of tumours with moderate CTA expression, while leukaemia could be considered to have a low CTA expression. Over 90 CTAs have been found in LC [25], and the majority of NSCLC patient samples (79%) expressed at least one of the analysed CTAs, with CTA protein levels corresponding with gene transcription [20]. CTA transcription was significantly related to the pathological N and TNM stages.…”

“…Tumour-associated antigens (TAA) are highly expressed in LC, but they also have elevated expression in other benign lung diseases and therefore have low specificity [18,19]. Due to the increase in TAA expression in benign lung diseases, the standard cut-off of biomarkers has to be doubled [20] to maximise the diagnostic yield of LC when differentiating between malignant and benign disease. Such cut-off levels have no benefit in imaging studies when using methods such as computer tomography (CT) scans in patients suspected of LC.…”

Melanoma Antigen Family A (MAGE A) as Promising Biomarkers and Therapeutic Targets in Bladder Cancer

“…In the past decade, the search for diverse biomarkers involved in cancer initiation and/or its progression led to the discovery of cancer-testis antigens (CTAs) as a breakthrough in cancer biology and clinical oncology [8][9][10]. CTAs are commonly expressed in various tumor types but have limited expression patterns in normal tissues; therefore, they are proposed as cancer biomarkers for diagnosis [11][12][13][14][15]. Some of these molecules are progressively increased during carcinogenesis and thus recognized as prognostic markers; both could be effective targets for prevention and/or therapeutic intervention.…”