Analysis of p53 Serum Antibodies in Patients With Head and Neck Squamous Cell Carcinoma

Bourhis, Jean; Lubin, R.; Roche, B.; Koscielny, Serge; Bosq, Jacques; Dubois, Isabelle; Talbot, Monique; Marandas, P.; Schwaab, G; Wibault, P.; Luboinski, B.; Eschwège, F.; Soussi, Thierry

doi:10.1093/jnci/88.17.1228

Cited by 82 publications

(46 citation statements)

References 28 publications

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“…P53-specific IgG antibodies have been found in patients with HNSCC and this was suggested to be linked with bad prognosis. 11,12 These p53-specific IgG responses indicate that p53-specific CD4þ T cells are also present in these patients. Indeed, the presence of both circulating and tumor-infiltrating p53-specific T cells has been reported.…”

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confidence: 85%

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Systemic and local human papillomavirus 16‐specific T‐cell immunity in patients with head and neck cancer

Heusinkveld

Goedemans

Briët

et al. 2011

Intl Journal of Cancer

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Squamous cell carcinomas of the head and neck (HNSCC), in particular those of the oropharynx, can be caused by human papilloma virus Type 16 (HPV16). Whereas these HPV-induced oropharyngeal carcinomas may express the HPV16 E6 and E7 oncoproteins and are associated with better survival, the nonvirally induced HNSCC are associated with overexpression of p53. In this study we assessed the presence of systemic and local T cells reactive against these oncoproteins in HNSCC. An exploratory study on the presence, type and function of HPV16-and/or p53-specific T cells in the blood, tumor and/or metastatic lymph node as measured by several immune assays was performed in an unselected group of 50 patients with HNSCC. Tumor tissue was tested for HPV DNA and the overexpression of p53 protein. Almost all HPV161 tumors were located in the oropharynx. Circulating HPV16-and p53-specific T cells were found in 17/47 and 7/45 tested patients. T cells were isolated from tumor cultures and/or lymph nodes of 20 patients. HPV16-specific T cells were detected in six of eight HPV1 tumors, but in none of the 12 HPV-tumors. Tumor-infiltrating p53-specific T cells were not detected. In depth analysis of the HPV16-specific T-cell response revealed that this response comprised a broad repertoire of CD41 T-helper Type 1 and 2 cells, CD41 regulatory T cells and CD81 T cells reactive to HPV16. The local presence of HPV16-specific T-cell immunity in HPV16-induced HNSCC implicates a role in the antitumor response and support the development of immunotherapy for HNSCC.

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confidence: 85%

“…In all cultures, both CD8þ and CD4þ T cells grew out (CD4/CD8 ratio median 2.45, average 5.1 and range 0. [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19]. The composition of T cells was not clearly influenced by the culture conditions (Fig.…”

Section: Hpv-specific T Cells Can Be Isolated From Oropharyngeal Tumomentioning

confidence: 99%

Systemic and local human papillomavirus 16‐specific T‐cell immunity in patients with head and neck cancer

Heusinkveld

Goedemans

Briët

et al. 2011

Intl Journal of Cancer

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“…More recently, serum antibodies reacting with the p53 protein have been detected in cancer patients with a variety of neoplasms (Schlichtholz et al, 1992;Angelopoulou et al, 1994Angelopoulou et al, , 1996Volkmann et al, 1993;Houbiers et al, 1995;Lubin et al, 1995a, b;Bourhis et al, 1996;Coomber et al, 1996;Gadducci et al, 1996;Ryder et al, 1996;Wild et al, 1995). A prerequisite for a B-cell response seems to be the accumulation in the tumour of a mutant or, less frequently, a wild-type p53 protein.…”

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confidence: 99%

“…A prerequisite for a B-cell response seems to be the accumulation in the tumour of a mutant or, less frequently, a wild-type p53 protein. Anti-p53 serum antibodies have been associated with poor prognosis and advanced stage in breast (Schlichtholz et al, 1992;Angelopoulou et al, 1996), head and neck (Bourhis et al, 1996), colorectal (Houbiers et al, 1995;Coomber et al, 1996) and ovarian (Angelopoulou et al, 1996;Gadducci et al, 1996) cancers. However, serological assessment of anti-p53 antibodies seems also to allow detection of tumours at an early and therefore more treatable stage (Lubin et al, 1995b;Trivers et al, 1995Trivers et al, , 1996.…”

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confidence: 99%

Clinical significance of circulating anti-p53 antibodies in European patients with hepatocellular carcinoma

et al. 1999

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Summary p53 alterations are considered to be predictive of poor prognosis in hepatocellular carcinoma (HCC) and may induce a humoral response. Anti-p53 serum antibodies were assessed by enzyme-linked immunosorbent assay (ELISA) using purified recombinant human p53 on 130 European HCC patients before treatment and during the clinical course of the disease. p53 immunohistochemistry was performed on tumours from the 52 patients who underwent surgery, and DNA sequencing analysis was initiated when circulating anti-p53 antibodies were detected. Nine (7%) HCC patients had anti-p53 serum antibodies before treatment. During a mean period of 30 months of follow-up, all the negative patients remained negative, even when recurrence was observed. Of the nine positive patients, eight were still positive 12-30 months after surgery. The presence of anti-p53 serum antibodies was correlated neither with mutation of the p53 gene nor the serum alphafetoprotein levels and clinicopathological characterics of the tumours. However, a greater incidence of vascular invasion and accumulation of p53 protein were observed in the tumours of these patients (P < 0.03 and P < 0.01 respectively) as well as a better survival rate without recurrence (P = 0.05). In conclusion, as was recently shown in pancreatic cancer, anti-p53 serum antibodies may constitute a marker of relative 'good prognosis' in a subgroup of patients exhibiting one or several markers traditionally thought to be of bad prognosis.

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“…[28][29][30][31][32] Antibody responses are Th2 cytokine-biased, which can downmodulate CTL-mediated anti-tumor responses and tumor eradication. 33,34 In many instances, anti-p53 antibody responses have been shown to decrease following surgical intervention.…”

Section: Discussionmentioning

confidence: 99%

Immunological characterization of missense mutations occurring within cytotoxic T cell‐defined p53 epitopes in HLA‐A*0201⁺ squamous cell carcinomas of the head and neck

Ito

Visús

Hoffmann³

et al. 2007

Intl Journal of Cancer

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Previous analyses of p53 in 40 HLA-A*0201(HLA-A2) 1 squamous cell carcinomas of the head and neck (SCCHN) indicated that 6/13 p53 missense mutations that were detected, S149C, T150R, V157F, Y220C, Y220H and E271K, occurred within HLA-A2-restricted cytotoxic T lymphocyte (CTL)-defined p53 epitopes. Of the 6, the p53 S149C, Y220C and Y220H peptides were immunogenic. Anti-p53 mutant S149C and Y220H effector cells crossreacted against the parental wild type sequence (wt) p53 peptides, whereas anti-p53 Y220C effector cells were specific for the mutant peptide, p53 Y220C cDNA-transfected HLA-A2 1 SaOS cells, and an HLA-A2 1 SCCHN cell line naturally expressing the mutation. These results indicate that the p53 Y220C mutation can be processed and presented for CD8 1 T cell recognition. Furthermore, using an autologous PBMC/tumor system, anti-p53 Y220C peptide-effector cells recognizing the autologous tumor could also be generated. Our analysis of p53 in 10 additional HLA-A2 1 SCCHN tumors detected the p53 Y220C in 2/10 tumors raising the overall frequency of the p53 Y220C mutation to 6/50 (12%) HLA-A2 1 SCCHN tumors. In contrast, independent of their HLA class I genotypes, the p53 Y220C mutation frequency for all human tumors analyzed to date is 1.5%. This unexpectedly high frequency of the p53 Y220C mutation in HLA-A2 1 SCCHN suggests that vaccines targeting this mutation would not only be expected to induce robust anti-tumor immune responses in HLA-A2 1 subjects, but also be more widely applicable than previously envisioned for any given p53 missense mutation. ' 2007 Wiley-Liss, Inc.

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Analysis of p53 Serum Antibodies in Patients With Head and Neck Squamous Cell Carcinoma

Abstract: The proportion of patients with HNSCC who have serum p53-Abs is smaller than that of patients exhibiting tumor cell accumulation of p53 protein. The presence of p53-Abs is significantly associated with increased risks of relapse and death.

Cited by 82 publications

References 28 publications

Systemic and local human papillomavirus 16‐specific T‐cell immunity in patients with head and neck cancer

Systemic and local human papillomavirus 16‐specific T‐cell immunity in patients with head and neck cancer

Clinical significance of circulating anti-p53 antibodies in European patients with hepatocellular carcinoma

Immunological characterization of missense mutations occurring within cytotoxic T cell‐defined p53 epitopes in HLA‐A*0201⁺ squamous cell carcinomas of the head and neck

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Analysis of p53 Serum Antibodies in Patients With Head and Neck Squamous Cell Carcinoma

Abstract: The proportion of patients with HNSCC who have serum p53-Abs is smaller than that of patients exhibiting tumor cell accumulation of p53 protein. The presence of p53-Abs is significantly associated with increased risks of relapse and death.

Cited by 82 publications

References 28 publications

Systemic and local human papillomavirus 16‐specific T‐cell immunity in patients with head and neck cancer

Systemic and local human papillomavirus 16‐specific T‐cell immunity in patients with head and neck cancer

Clinical significance of circulating anti-p53 antibodies in European patients with hepatocellular carcinoma

Immunological characterization of missense mutations occurring within cytotoxic T cell‐defined p53 epitopes in HLA‐A*0201+ squamous cell carcinomas of the head and neck

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Immunological characterization of missense mutations occurring within cytotoxic T cell‐defined p53 epitopes in HLA‐A*0201⁺ squamous cell carcinomas of the head and neck