Affiliation:
1. Department of Immunology, Genetics and Pathology, Rudbeck Laboratory Uppsala University Sweden
2. Department of Medicine (Medical Oncology) Yale University School of Medicine New Haven CT USA
3. Division of Pathology, Department of Clinical Sciences Lund Lund 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.
Funder
Cancerfonden
Knut och Alice Wallenbergs Stiftelse
Lions Clubs International Foundation
Sjöbergstiftelsen
Vetenskapsrådet
Subject
Cancer Research,Genetics,Molecular Medicine,General Medicine,Oncology
Cited by
1 articles.
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