Expression of cancer-testis antigens in the immune microenvironment of non-small cell lung cancer
Feria Hikmet1, Marc Rassy1, Max Backman1
1Department of Immunology, Genetics and Pathology, Rudbeck Laboratory, Uppsala University, Sweden.
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.
Insights
Cancer-testis antigens (CTAs) are expressed in most non-small cell lung cancers (NSCLC). CTA expression correlates with immune cell infiltration, suggesting potential as immunotherapy targets.
Area of Science:
- Oncology
- Immunology
- Genetics
Background:
- Tumor antigenic repertoire is crucial for anti-cancer immunity and immunotherapy efficacy.
- Cancer-testis antigens (CTAs) are recognized by both humoral and cellular immune responses.
- Understanding CTA expression in non-small cell lung cancer (NSCLC) is vital for developing targeted therapies.
Purpose of the Study:
- To characterize the expression of eight selected CTAs in NSCLC.
- To investigate the association between CTA expression and the tumor immune microenvironment.
- To explore correlations between CTA profiles, genomic, transcriptomic, and clinical data.
Main Methods:
- RNA sequencing to validate 90 CTAs.
- Immunohistochemical profiling of eight CTAs (DPEP3, EZHIP, MAGEA4, MAGEB2, MAGEC2, PAGE1, PRAME, TKTL1) in 328 NSCLC patient tissues.
- Comparison of CTA expression with immune cell densities and clinical data.
Main Results:
- 79% of NSCLC cases expressed at least one of the analyzed CTAs.
- CTA protein expression generally correlated with RNA expression.
- Specific CTA profiles were associated with distinct immune cell infiltrations (e.g., MAGEA4 with M2 macrophages and regulatory T cells; EZHIP with plasma cells).
Conclusions:
- CTA expression is prevalent in NSCLC and linked to specific immune microenvironment features.
- These associations suggest potential in situ immunogenic roles for CTAs.
- CTAs represent promising targets for NSCLC immunotherapy development.
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