Immune response, inflammation pathway gene polymorphisms, and the risk of cervical cancer

The local immune response is considered a key determinant in cervical carcinogenesis after persistent infection with oncogenic, high-risk human papillomavirus (HPV) infections. Genetic variation in various immune response genes has been shown to influence risk of developing cervical cancer, as well as progression and survival among cervical cancer patients. We reviewed the literature on associations of immunogenetic single nucleotide polymorphism, allele, genotype, and haplotype distributions with risk and progression of cervical cancer. Studies on HLA and KIR gene polymorphisms were excluded due to the abundance on literature on that subject. We show that multiple genes and loci are associated with variation in risk of cervical cancer. Rather than one single gene being responsible for cervical carcinogenesis, we postulate that variations in the different immune response genes lead to subtle differences in the effectiveness of the antiviral and antitumour immune responses, ultimately leading to differences in risk of developing cervical cancer and progressive disease after HPV infection.

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Immune response gene polymorphisms in tuberculosis

Acta Biochimica Polonica ◽

10.18388/abp.2015_1130 ◽

2015 ◽

Vol 62 (4) ◽

pp. 633-640 ◽

Cited By ~ 14

Author(s):

Marek Fol ◽

Magdalena Druszczynska ◽

Marcin Wlodarczyk ◽

Elzbieta Ograczyk ◽

Wieslawa Rudnicka

Keyword(s):

Immune Response ◽

Gene Polymorphisms ◽

Immune Response Gene ◽

Response Gene

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A case–control study of innate immunity pathway gene polymorphisms in Puerto Ricans reveals association of toll-like receptor 2 +596 variant with asthma

BMC Pulmonary Medicine ◽

10.1186/s12890-016-0272-7 ◽

2016 ◽

Vol 16 (1) ◽

Cited By ~ 3

Author(s):

Mario G. Ortiz-Martínez ◽

Orquídea Frías-Belén ◽

Sylvette Nazario-Jiménez ◽

María López-Quintero ◽

Rosa I. Rodríguez-Cotto ◽

...

Keyword(s):

Innate Immunity ◽

Gene Polymorphisms ◽

Case Control Study ◽

Puerto Ricans ◽

Case Control ◽

Toll Like Receptor ◽

Pathway Gene ◽

Toll Like Receptor 2 ◽

Innate Immunity Pathway ◽

Control Study

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Human Papillomavirus Type 16 E7 Peptide-Directed CD8+ T Cells from Patients with Cervical Cancer Are Cross-Reactive with the Coronavirus NS2 Protein

Journal of Virology ◽

10.1128/jvi.77.9.5464-5474.2003 ◽

2003 ◽

Vol 77 (9) ◽

pp. 5464-5474 ◽

Cited By ~ 53

Author(s):

Katja Nilges ◽

Hanni Höhn ◽

Henryk Pilch ◽

Claudia Neukirch ◽

Kirsten Freitag ◽

...

Keyword(s):

Cervical Cancer ◽

Immune Response ◽

T Cells ◽

Human Papillomavirus ◽

T Cell ◽

T Cell Responses ◽

Cross Reactivity ◽

Antiviral Immune Response ◽

Human Papillomavirus Type 16 ◽

Cell Responses

ABSTRACT Human papillomavirus type 16 (HPV16) E6 and E7 oncoproteins are required for cellular transformation and represent candidate targets for HPV-specific and major histocompatibility complex class I-restricted CD8+-T-cell responses in patients with cervical cancer. Recent evidence suggests that cross-reactivity represents the inherent nature of the T-cell repertoire. We identified HLA-A2 binding HPV16 E7 variant peptides from human, bacterial, or viral origin which are able to drive CD8+-T-cell responses directed against wild-type HPV16 E7 amino acid 11 to 19/20 (E711-19/20) epitope YMLDLQPET(T) in vitro. CD8+ T cells reacting to the HLA-A2-presented peptide from HPV16 E711-19(20) recognized also the HLA-A2 binding peptide TMLDIQPED (amino acids 52 to 60) from the human coronavirus OC43 NS2 gene product. Establishment of coronavirus NS2-specific, HLA-A2-restricted CD8+-T-cell clones and ex vivo analysis of HPV16 E7 specific T cells obtained by HLA-A2 tetramer-guided sorting from PBL or tumor-infiltrating lymphocytes obtained from patients with cervical cancer showed that cross-reactivity with HPV16 E711-19(20) and coronavirus NS252-60 represents a common feature of this antiviral immune response defined by cytokine production. Zero of 10 patients with carcinoma in situ neoplasia and 3 of 18 patients with cervical cancer showed ≥0.1% HPV16 E7-reactive T cells in CD8+ peripheral blood lymphocytes. In vivo priming with HPV16 was confirmed in patients with cervical cancer or preinvasive HPV16-positive lesions using HLA-A2 tetramer complexes loaded with the E6-derived epitope KLPQLCTEL. In contrast, we could not detect E6-reactive T cells in healthy individuals. These data imply that the measurement of the HPV16 E711-19(20) CD8+-T-cell response may reflect cross-reactivity with a common pathogen and that variant peptides may be employed to drive an effective cellular immune response against HPV.

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