The introduction of PD-1 blockades to chemotherapy and radiotherapy has shown promising outcomes in patients with nasopharyngeal carcinoma, but anti-PD-1 therapies are only effective in a small proportion of patients, indicating the need for reliable predictive biomarkers of benefit from immunotherapy. Here, we summarized recent advances in immunotherapy for nasopharyngeal carcinoma and studies on potential predictors that correlated with treatment response or long-term survival after immunotherapy, including biomarkers in both the tumor microenvironment and the tumor macroenvironment. Some of these biomarkers have been validated as truly predictive of immunotherapy benefit using cohorts from randomized controlled trials, while others still require further validation of their predictive value. We also summarized the challenges and future directions of biomarker studies, hopefully facilitating the development of predictive biomarkers for immunotherapy that can eventually enter clinical practice.
Humans ; Tumor Microenvironment/immunology* ; Nasopharyngeal Carcinoma/immunology* ; Immunotherapy/methods* ; Nasopharyngeal Neoplasms/immunology* ; Biomarkers, Tumor/metabolism* ; Immune Checkpoint Inhibitors/therapeutic use*

Objective: To evaluate the safety and effectiveness of a vaccine based on latent membrane protein 2 (LMP2) modified dendritic cells (DCs) that boosts specific responses of cytotoxic T lymphocytes (CTLs) to LMP2 before and after intradermal injection in patients with nasopharyngeal carcinoma (NPC). Methods: DCs were derived from peripheral blood monocytes of patients with NPC. We prepared LMP2-DCs infected by recombinant adenovirus vector expressing LMP2 (rAd-LMP2). NPC patients were immunized with 2 × 10 Results: We demonstrated that DCs derived from monocytes displayed typical DC morphologies; the expression of LMP2 in the LMP2-DCs vaccine was confirmed by immunocytochemical assay. Twenty-nine patients with NPC were enrolled in this clinical trial. The LMP2-DCs vaccine was well tolerated in all of the patients. Boosted responses to LMP2 peptide sub-pools were observed in 18 of the 29 patients with NPC. The follow-up data of 29 immunized patients from April, 2010 to April 2015 indicated a five-year survival rate of 94.4% in responders and 45.5% in non-responders. Conclusion In this pilot study, we demonstrated that the LMP2-DCs vaccine is safe and effective in patients with NPC. Specific CTLs responses to LMP2 play a certain role in controlling and preventing the recurrence and metastasis of NPC, which warrants further clinical testing.
Adult ; Aged ; Cancer Vaccines/therapeutic use* ; China ; Dendritic Cells/immunology* ; Female ; Humans ; Immunotherapy/methods* ; Injections, Intradermal ; Male ; Middle Aged ; Nasopharyngeal Carcinoma/therapy* ; Nasopharyngeal Neoplasms/therapy* ; T-Lymphocytes, Cytotoxic/immunology* ; Viral Matrix Proteins/therapeutic use* ; Young Adult

Autoantigens ; metabolism ; Glycoproteins ; metabolism ; Humans ; Immunity, Innate ; immunology ; Lactoferrin ; metabolism ; Nasopharyngeal Carcinoma ; immunology ; metabolism ; Nasopharyngeal Neoplasms ; immunology ; metabolism ; Phosphoproteins ; metabolism ; Proteins ; metabolism

BackgroundDevelopment of innovative immunotherapy is imperative to improve the poor survival of the nasopharyngeal carcinoma (NPC) patients. In this study, we evaluated the T cell response to melanoma-associated antigen (MAGE)-A1, MAGE-A3, or synovial sarcoma X-2 (SSX-2) in the peripheral blood of treatment-naive NPC patients. The relationship of responses among the three proteins and the human leukocyte antigen (HLA)-A types were analyzed to provide evidence of designing novel therapy.

MethodsSixty-one NPC patients admitted into the Tumor Hospital affiliated to the Xinjiang Medical University between March 2015 and July 2016 were enrolled. Mononuclear cells were isolated from the peripheral blood before any treatment. HLA-A alleles were typed with Sanger sequence-based typing technique. The T cell response to the MAGE-A1, MAGE-A3, or SSX-2 was evaluated with the Enzyme-Linked ImmunoSpot assay. Mann-Whitney U-test was used to compare the T cell responses from different groups. Spearman's rank correlation was used to analyze the relationship of T cell responses.

ResultsHLA-A*02:01, A*02:07, and A*24:02 were the three most frequent alleles (18.9%, 12.3%, and 11.5%, respectively) among the 22 detected alleles. 31.1%, 19.7%, and 16.4% of the patients displayed MAGE-A1, MAGE-A3, or SSX-2-specific T cell response, respectively. The magnitudes of response to the three proteins were 32.5, 38.0, and 28.7 SFC/10 peripheral blood mononuclear cells, respectively. The T cell response against the three proteins correlated with each other to different extent. The percentage of A*02:01 and A*24:02 carriers were significantly higher in patients responding to any of the three proteins compared to the nonresponders.

ConclusionMAGE-A1, MAGE-A3, or SSX-2-specific T cell responses were detectable in a subgroup of NPC patients, the frequency and magnitude of which were correlated.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Alleles ; Antigens, Neoplasm ; immunology ; metabolism ; Carcinoma ; immunology ; metabolism ; Female ; HLA-A Antigens ; metabolism ; Humans ; Leukocytes, Mononuclear ; metabolism ; Male ; Middle Aged ; Nasopharyngeal Carcinoma ; Nasopharyngeal Neoplasms ; immunology ; metabolism ; Neoplasm Proteins ; metabolism ; Sarcoma, Synovial ; immunology ; metabolism ; Young Adult

OBJECTIVETo explore the incidence regularity in populations with different fluctuation modes of Epstein-Barr virus (EBV) antibody levels.

METHODSBased on the data of a NPC mass screening for nasopharyngeal carcinoma (NPC) in Jianggu town and Didou town of Sihui city, Guangdong province from 1992 to 1998, 586 subjects who were positive and retested for twice or above were divided into ascending group (114 subjects), stable or fluctuating group (313 subjects), and descending group (159 subjects) according to the fluctuation of immunoglobulin A antibody against EBV capsid antigen (VCA-IgA) level; 9889 subjects who were negative in the first test of VCA-IgA were set as control group. All the participants were followed-up till December 31, 2007. The incidence, onset time and clinical characteristics of NPC were compared among groups.

RESULTSThe 5-year cumulative detection rates of ascending, stable or fluctuating, and descending group were 3.51% (4/114), 0.64% (2/313) and 0.00% (0/159), respectively; the 5-year cumulative detection proportions were 4/4, 2/6 and 0/2, respectively. Comparing to the control group, the hazard ratio (HR) for the incidence of NPC in ascending group was highest (HR = 10.96, 95%CI: 3.91 - 30.74), followed by stable or fluctuating group (HR = 5.79, 95%CI: 2.45 - 13.69), and descending group (HR = 3.84, 95%CI: 0.92 - 16.01) which had the lowest HR.

CONCLUSIONIndividuals with stable, fluctuating or ascending VCA-IgA level showed higher risk and earlier onset of NPC was found in ascending group.

Adult ; Antibodies, Viral ; blood ; Antigens, Viral ; immunology ; Capsid Proteins ; immunology ; Carcinoma ; China ; epidemiology ; Female ; Humans ; Immunoglobulin A ; blood ; Incidence ; Male ; Middle Aged ; Nasopharyngeal Neoplasms ; blood ; diagnosis ; epidemiology

OBJECTIVETo explore the clinical significance of cytokeratin 19 fragments test in the diagnosis of nasopharyngeal carcinoma.

METHODSThe study included 102 cases of nasopharyngeal carcinoma, 90 cases of nasal polyp/nasopharyngitis, and 150 healthy individuals. RT-PCR was used to detect CK19 mRNA expression and Western blot to detect CK19 fragment protein expression in tissues of nasopharyngeal carcinoma. Expression of CK19-2G2 was examined by immunohistochemistry. Chemiluminescence analysis was used to detect the serum levels of CK19-2G2, and ELISA to detect that of EB-VCA IgA.

RESULTSAmong 102 cases of nasophryngeal carcinoma, 64 showed CK19 mRNA expression by RT-PCR, 60 showed CK19 protein fragments in tumor tissues by Western blot, and 66 showed expression of CK19-2G2 by immunohistochemistry in nasopharyngeal carcinoma, including strong positivity in 20 cases, moderate in 34 cases and weak in 12 cases. The sensitivity and specificity of CK19-2G2 in the diagnosis of nasopharyngeal carcinoma were 49.0% and 89.2%, and those of EB-VCA IgA were 52.9% and 85.4%, respectively. The combined detection of CK19-2G2 and EB-VCA IgA increased the sensitivity to 73.5% while the specificity remained at 80.0%.

CONCLUSIONSHigh levels of CK19-2G2 fragment expressed in tissue and serum are present in patients with nasopharyngeal carcinoma. The serum level of CK19-2G2 is helpful in the diagnosis of nasopharyngeal carcinoma. Furthermore, the combination of serum CK19-2G2 and EB-VCA IgA improves the detection sensitivity.

Adult ; Aged ; Antigens, Viral ; blood ; Blotting, Western ; Capsid Proteins ; blood ; Carcinoma, Squamous Cell ; diagnosis ; metabolism ; pathology ; Herpesvirus 4, Human ; immunology ; Humans ; Immunoglobulin A ; blood ; Immunohistochemistry ; Keratin-19 ; blood ; metabolism ; Middle Aged ; Nasopharyngeal Neoplasms ; diagnosis ; metabolism ; pathology ; Neoplasm Staging ; Peptide Fragments ; blood ; metabolism ; RNA, Messenger ; metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Sensitivity and Specificity

OBJECTIVE: To investigate the tumor regression and local immune function in nasopharyngeal carcinoma patients treated with p53 gene therapy. METHOD: The two-step immunohistochemical was done to detect the expression of tumor-infiltrating lymphocytes (TIL) T-cell receptor-CD3, CD4, CD8 and B cell receptor-CD20 in the primary tumor tissue of nasopharyngeal carcinoma. Nasal endoscopy with MRI or CT was used for evaluation of tumor size. RESULT: The expression of CD3, CD4, CD8 was significantly increased after p53 gene treatment (P < 0.05). There was no significant change in expression of CD20 after p53 gene treatment (P > 0.05). In conventional treatment group, CD3, CD4, CD8 and CD20 (P > 0.05) did not show any significant difference. In gene therapy group at 3 months after treatment, 20 patients had achieved CR, 10 PR, 1 SD, 1 PD. In conventional treatment group, 11 patients had achieved CR, 12 PR,5 SD,3 PD. The response rate between treatment group and control group (CR+PR) was different (P < 0.05). CD3 and CD4 expression was correlated with tumor regression rate (P < 0.05, P < 0.01), and CD8 expression was correlated with the CR rate (P < 0.05). CONCLUSION T cells are the most proliferative cell of TII. in NPC patients after p53 gene therapy The local cellular immune status is positively correlated with tumor regression rate.
Adult ; Aged ; CD4-Positive T-Lymphocytes ; immunology ; Carcinoma ; Female ; Genes, p53 ; Genetic Therapy ; Humans ; Lymphocyte Count ; Lymphocytes, Tumor-Infiltrating ; immunology ; Male ; Middle Aged ; Nasopharyngeal Carcinoma ; Nasopharyngeal Neoplasms ; immunology ; pathology ; therapy

OBJECTIVE: To investigate the effect of bi yan qing du ke li combined with Nasal Care on the titers of EB virus VCA/IgA and nasopharyngeal symptoms in patients with nasopharyngeal carcinoma(NPC) after radiotherapy. METHOD: Sixty NPC patients underwent-radiotherapy were randomly divided into study group (bi yan qing du ke li combined with nasal care, n=30) and control group (bi yan qing du ke li group, n=30). RESULT: After treatment, the geometric mean titer of VCA/IgA was 20.5 in study group and 55.6 in control group, respectively (P < 0.05). Meanwhile, the nasopharyngeal symptoms after treatment in study group was improved significantly better than that of control group (P < 0.05). CONCLUSION The application of bi yan qing du ke li combined with Nasal Care can significantly decrease the titers of VCA/IgA in NPC patients after-radiotherapy and improve the nasopharyngeal symptoms, which might be helpful to decrease the recurrence rate of NPC.
Adult ; Aged ; Antibodies, Viral ; blood ; immunology ; Antigens, Viral ; blood ; immunology ; Capsid Proteins ; blood ; immunology ; Carcinoma ; Combined Modality Therapy ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Humans ; Immunoglobulin A ; blood ; immunology ; Male ; Middle Aged ; Nasopharyngeal Carcinoma ; Nasopharyngeal Neoplasms ; immunology ; radiotherapy ; therapy ; Prognosis

In a prospective study, 42 048 adults residing in Zhongshan City, Guangdong, China, were followed for 16 years, and 171 of them developed nasopharyngeal carcinoma (NPC). Although Epstein-Barr virus (EBV) antibody levels of the cohort fluctuated, the antibody levels of 93% of the patients with NPC were raised and maintained at high levels for up to 10 years prior to diagnosis. This suggests that the serologic window affords an opportunity to monitor tumor progression during the preclinical stage of NPC development, facilitating early NPC detection. We reviewed the clinical records of the 171 patients with NPC in the prospective study to assess the efficacy of early NPC detection by serologic screening and clinical examination. Of the 171 patients, 51 had Stage I tumor (44 were among the 73 patients detected by clinical examination and 7 were among the 98 patients presented to outpatient department). Initial serologic screening predicted 58 (95.1%) of the 61 patients detected within 2 years. The risk of the screened population (58/3093) raised 13 times relative to cohort (61/42 048) during this period. Clinical examination detected all the 58 predicted cases, and 35 (60.3%) of which were diagnosed with Stage I tumor. The serologic prediction rate fell to 33.6% (37/110) 2 to 16 years after screening. The proportion of cases detected by clinical examination fell to 40.5% (15/37). The proportion of Stage I tumors among the cases detected by clinical examination during both periods remained at about 60%. We concluded that early detection of NPC can be accomplished by repeated serologic screening to maintain high prediction rates and by promptly examining screened subjects to detect tumors before the symptoms develop.
Adult ; Aged ; Antibodies, Viral ; blood ; Antigens, Viral ; immunology ; Capsid Proteins ; immunology ; Carcinoma, Squamous Cell ; blood ; diagnosis ; pathology ; Chemotherapy, Adjuvant ; Cohort Studies ; Early Detection of Cancer ; methods ; Female ; Herpesvirus 4, Human ; immunology ; Humans ; Male ; Middle Aged ; Nasopharyngeal Neoplasms ; blood ; diagnosis ; pathology ; Neoplasm Metastasis ; Neoplasm Recurrence, Local ; Neoplasm Staging ; Remission Induction ; Survival Rate

Nasopharyngeal carcinoma (NPC) has remarkable epidemiological features, including regional, racial, and familial aggregations. The aim of this review is to describe the epidemiological characteristics of NPC and to propose possible causes for the high incidence patterns in southern China. Since the etiology of NPC is not completely understood, approaches to primary prevention of NPC remain under consideration. This situation highlights the need to conduct secondary prevention, including improving rates of early detection, early diagnosis, and early treatment in NPC patients. Since the 1970's, high-risk populations in southern China have been screened extensively for early detection of NPC using anti-Epstein-Barr virus (EBV) serum biomarkers. This review summarizes several large screening studies that have been conducted in the high-incidence areas of China. Screening markers, high-risk age range for screening, time intervals for blood re-examination, and the effectiveness of these screening studies will be discussed. Conduction of prospective randomized controlled screening trials in southern China can be expected to maximize the cost-effectiveness of early NPC detection screening.
Age Factors ; Antibodies, Viral ; analysis ; Antigens, Viral ; analysis ; Asian Continental Ancestry Group ; genetics ; Capsid Proteins ; analysis ; Carcinoma ; China ; epidemiology ; Early Detection of Cancer ; methods ; Herpesvirus 4, Human ; immunology ; Humans ; Nasopharyngeal Neoplasms ; epidemiology ; genetics ; immunology ; prevention & control ; Prevalence