High endothelial venules are present in pharyngeal and laryngeal carcinomas and they are associated with better prognosis.

BACKGROUND: Tumors lymphocytic infiltration has prognostic and predictive value. However, the mechanisms involved in lymphocyte recruitment remain poorly characterized. High endothelial venules (HEV) are blood vessels specialized in lymphocyte recruitment, recently showing prognostic significance in some types of cancer. Their implications in laryngeal or pharyngeal cancer is largely unknown. AIM OF THE STUDY: To investigate the possible presence of HEVs in head and neck cancer. MATERIAL AND METHODS: Oropharyngeal (n = 61), hypopharyngeal (n = 53) and laryngeal (n = 21) squamous cell carcinomas were immunohistochemically studied with the MECA-79 antibody, which specifically recognizes HEVs. Histological and clinical factors were correlated with HEVs' presence. RESULTS: HEVs were present in 34% of tumors, showing significant correlations with oropharyngeal localization, higher lymphocytic response, lower tumor budding, lower T status, absence of distant metastases and better overall and progression-free survival. CONCLUSION: HEVs represent an important prognostic factor in head and neck cancer.

Association of autoimmunity with survival in patients with recurrent/metastatic head and neck squamous cell carcinoma treated with nivolumab.

OBJECTIVES: Immune checkpoint inhibitors (ICIs) are associated with immune-related adverse events (irAEs) that occur as a consequence of enhanced immune response due to T-cell activation. The objective of this retrospective study was to investigate the association between irAEs and disease outcome in patients with recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC). MATERIALS AND METHODS: This study included 89 patients with R/M HNSCC who were treated with nivolumab in our center from October 2015 to January 2020. Overall survival (OS) and post-progression survival (PPS) were calculated from the date of nivolumab initiation or from the date of progression on nivolumab respectively to the date of death or censored at the last date of follow up. RESULTS: Twenty-four patients (27%) developed irAEs, with more common thyroiditis (N = 13, 14.6%). ORR did not differ between patients with irAEs (29.2%) and patients without irAEs (21.9%, p = 0.576). Median PFS was similar between the two groups (3.1 months for patients with irAEs vs. 2.6 months for patients without irAEs, p = 0.412). Median OS was significantly longer in patients with irAEs (17.9 vs. 6.3 months in patients without irAEs, log-rank p = 0.004). Additionally, median PPS was significantly improved in patients who developed irAEs (10.2 months vs. 2.8 months for patients without irAEs, log-rank p = 0.001). In multivariate analysis, the development of irAEs and response to nivolumab were shown to be independent prognostic factors for favorable OS and PPS. CONCLUSIONS: The development of irAEs is a strong predictor of improved survival in patients with advanced HNSCC treated with nivolumab.

Systemic immune response associated with radiation therapy in B­cell non­Hodgkin's lymphoma of Waldeyer's ring.

Radiation therapy (RT) is one of the most effective therapeutic modalities for B­cell non­Hodgkin's lymphoma of Waldeyer's ring (WR­B­NHL). However, the responsiveness of RT remains controversial and clinical biomarkers are required to predict survival in RT­treated patients with WR­B­NHL. Previous studies have suggested an association between RT and systemic immune responses. In the present retrospective study, the lymphocyte to monocyte ratio (LMR) was identified as a systemic immune indicator in RT­treated patients with WR­B­NHL, and the prognostic value of the LMR with RT and systemic immune responses were evaluated. The optimal cut­off value of the LMR was selected as 3.14, and a high LMR demonstrated improved prognosis and was considered an independent prognostic indicator in RT­treated patients, particularly in patients with distant non­irradiated lesions. Furthermore, reverse transcription­quantitative polymerase chain reaction and ELISA analysis of irradiated lymphoma cell lines and serum samples from patients with WR­B­NHL demonstrated the upregulated expression levels of 4­1BB ligands, calreticulin and high mobility group box 1 compared with non­irradiated groups. Additionally, CD8+ T cells and expression levels of interferon­Î³ in T cells co­cultured with irradiated cells were significantly increased compared with non­irradiated cells. The results indicated that the anti­programmed cell death protein 1 (PD­1) antibody may serve a role in lymphoma therapy when combined with RT. The results of the present study demonstrated the prognostic significance of the LMR associated with RT in patients with WR­B­NHL and acknowledged the potential use of PD­1 antibody in RT­treated lymphomas.

Risk of oral tongue cancer among immunocompromised transplant recipients and human immunodeficiency virus-infected individuals in the United States.

BACKGROUND: Oral tongue cancer incidence has increased among whites in the United States; however, the cause remains unknown. If an infectious agent is implicated, then elevated risk would be expected among immunosuppressed individuals. METHODS: By using population-based registry linkage information from the US Transplant Cancer Match and human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) Cancer Match studies, the authors examined the risk of oral tongue squamous cell carcinoma (SCC) among immunocompromised transplantation recipients and HIV-infected individuals. In addition, the risks of oropharyngeal SCC (strongly related to human papillomavirus infection; modestly affected by immunosuppression), other tobacco/alcohol-related oral cavity SCCs (not thought to be infection/immunosuppression-related), and non-Hodgkin lymphoma of oral cavity/pharynx (strongly related to Epstein-Barr virus; profoundly affected by immunosuppression) were evaluated. RESULTS: Compared with the general population, the risk of non-Hodgkin lymphoma was strongly increased (standardized incidence ratio [SIR] > 8.0). The risk of all SCCs was modestly and similarly elevated among transplantation recipients (SIR range, 2.2-2.7; Pheterogeneity = .2); whereas, among HIV-infected individuals, the risk of oral tongue SCC was higher compared with the risk of other SCCs (SIR, 3.0 vs 1.7 [for oropharyngeal SCCs] and 2.3 [for other oral cavity SCCs]; Pheterogeneity < .001). The risk of SCCs was significantly higher among men, older individuals, and whites; and risk increased with the time since transplantation/AIDS onset. The risk of oral tongue SCC was significantly higher among HIV-infected men who have sex with men compared with the average risk in HIV-infected individuals (adjusted incidence rate ratio = 2.0). CONCLUSIONS: Similar modest increases in the risk of oral tongue and other oral cavity SCCs do not suggest that an infectious agent or exposure profoundly affected by immunosuppression underlies the increase in oral tongue cancer. Cancer 2018;124:2515-22. © 2018 American Cancer Society.

Pediatric Pharyngeal IgD-positive Monoclonal Plasmacytoid and Plasma Cell Neoplasm.

Pediatric neoplasm with monoclonal proliferation of lymphoplasmacytoid lymphocytes and plasma cells is exceedingly rare and has essentially never been reported in immunocompetent children. Here, we report a previously healthy 13-year-old girl with a pharyngeal mass and enlarged cervical lymph nodes. The pharyngeal mass was composed of CD138, CD79a, MUM-1, IgD, CD20, PAX-5, CD43, λ-restricted monoclonal plasmacytoid, and plasma cells. Scattered CD20, PAX-5 B cells were present in the background. The patient was treated as localized non-Hodgkin lymphoma (stage II) with cyclophosphamide, doxorubicin, vincristine, and prednisone and is in complete remission at 17 months from the last chemotherapy.

Significance of serum antibodies against HSP 60 and HSP 70 for the diagnostic of infectious diseases.

Heat shock proteins (HSP) represent important antigenic targets for the immune response, playing an important role in the pathology and infectious diseases control. The purpose of this work was to investigate the levels of HSP60 and HSP70 specific antibodies in the bloodstream of patients with different bacterial infections and cancer, in order to evaluate their potential role as diagnosis markers of different infectious diseases. Detection of specific anti-HSP 60 and HSP 70 serum levels was performed by ELISA. Statistical analysis of data by multivariate logistic regression was performed using GraphPadPrism software and statistical tests based on chi-square and Student t-test. High levels of anti-HSP60 were found in patients with localized infections, while the levels of anti- HSP70 were higher in the group with generalized infections. The serum levels of both anti-HSP 60 and anti-HSP70 were significantly increased in patients with Gram-negative bacterial infections, as compared with patients harbouring infections produced by Gram-positive and fungal strains, demonstrating their potential use as additional diagnosis and prognosis markers in infections with this etiology.

Immunophenotypic and clinical differences between the nasal and extranasal subtypes of upper aerodigestive tract natural killer/T-cell lymphoma.

PURPOSE: To investigate, in a large cohort of patients, the immunophenotypic and clinical differences of nasal and extranasal extranodal nasal-type natural killer/T-cell lymphoma of the upper aerodigestive tract (UADT-NKTCL) and examine the relevance of the immunophenotype on the clinical behavior, prognosis, and treatment. METHODS AND MATERIALS: A total of 231 patients with UADT-NKTCL were recruited. One hundred eighty-one patients had primary location in the nasal cavity (nasal UADT-NKTCL), and 50 patients had primary extranasal UADT-NKTCL. RESULTS: Patients with extranasal UADT-NKTCL had more adverse clinical features, including advanced-stage disease, regional lymph node involvement, B symptoms, and poor performance status, than patients with nasal UADT-NKTCL. In addition, CD56 and granzyme B were less frequently expressed in extranasal UADT-NKTCL. The 5-year overall survival rate was 74.1% for the entire group and 76.0% for early-stage disease. The 5-year overall survival rate for extranasal UADT-NKTCL was similar or superior to that of nasal UADT-NKTCL for all disease stages (76.9% vs 73.4%, P=.465), stage I disease (75.9% vs 79.2%, P=.786), and stage II disease (83.3% vs 50.3%, P=.018). CD56 expression and a Ki-67 proliferation rate ≥ 50% predicted poorer survival for extranasal UADT-NKTCL but not for nasal UADT-NKTCL. CONCLUSIONS: Patients with nasal and extranasal UADT-NKTCL have significantly different clinical features, immunophenotypes, and prognosis. Extranasal UADT-NKTCL should be considered as a distinct subgroup apart from the most commonly diagnosed prototype of nasal UADT-NKTCL.

Pharyngolaryngeal location of Kaposi's sarcoma with airway obstruction in an HIV-negative patient.

Kaposi's sarcoma (KS) is a human herpes virus-8 (HHV-8)-associated angioproliferative disorder, and its occurrence may be favored by human immunodeficiency virus (HIV) infection and iatrogenic immunosuppression. It has also been postulated that a chronic inflammatory disease of the skin can pave the way to its development. KS generally involves mucosal and cutaneous sites, including the head and neck. An oropharyngeal location is quite common, but laryngeal involvement with possible upper airway obstruction and respiratory distress requiring tracheotomy is rare, and no hypopharyngeal locations have yet been reported. We describe the case of a 68-year-old male patient who developed KS after immunosuppressive treatment for pemphigus vulgaris, an autoimmune bullous disease presenting with blisters and erosions on the skin and the oral mucosa. KS was initially localized to the oral cavity and oropharynx, but subsequent involvement of the laryngeal and hypopharyngeal tract led to acute airway obstruction and the need for tracheotomy. This unique case of pharyngolaryngeal KS suggests that clinicians faced with purple nodular lesions should consider a differential diagnosis of KS in immunocompromised patients, even if they are HIV negative, and should carefully manage the patency of the upper airways.

Investigation of Th1/Th2 cytokine profiles in patients with laryngo-pharyngeal, HPV-positive cancers.

The aim of this study was to reveal the relationships between the features of the primary tumour, the degree of tumour stage, the presence of human papillomaviruses (HPV) in blood and the severity of Th1/Th2 serum cytokine imbalance in patients with laryngo-pharyngeal cancer. The study was performed on 50 patients (47 men and 3 women), with age ranging from 40 to 83 years (the mean of the patients' ages was 58.4 ± 9.43 years, with a median of 60 years). A control group was represented by age-matched healthy patients (with no clinical diseases). The viral DNA was detected by PCR; the cytokine levels were determined by ELISA. A clear switch from cytokine Th1 to cytokine Th2 in cancer patients, low levels of IL-2 and IFNγ in advanced stages, as well as a positive correlation of increased levels of both IL-2 and IL-12 with the early stages of laryngo-pharyngeal cancer was observed. Loco-regional metastases were correlated with increased levels of IL-8 and IL-10 and drastic decrease of IFNγ. In advanced cancer stages, we found that the most affected were IL-2 and IFNγ correlated with increased levels of Th2 cytokines. Patients with HPV present in both primary tumours and blood showed increased values of IL-4:IL-2 ratio as compared with patients with HPV-positive primary tumours only, demonstrating the aggravation of the immunosuppressive state. The most important finding of our study is that for a correct evaluation of the Th1 to Th2 switch in cancer patients, it is necessary to establish not only the negative/positive correlations between different Th1 and Th2 type cytokines, but also the ratio between them. These parameters allowed us to state that the presence of HPV DNA in blood was associated with the most severe immunological imbalance that could potentially lead to a poor prognosis of these patients. Our findings encourage us to consider that the ratio between different Th1 and Th2 cytokines could represent a useful marker for clinical and pathological evaluation of cancer patients.

[The involvement of RCAS1 in creating a suppressive tumor microenvironment in patients with pharyngeal squamous cell carcinoma]. / Udzial bialka RCAS1 w tworzeniu supresyjnego profilu mikrosrodowiska raka plaskonablonkowego gardla srodkowego.

INTRODUCTION: Tumor microenvironment makes up the stroma of the neoplasm and is the tissue that determines the growth and progression of the tumor and its ability to create metastases. THE AIM OF THE PRESENT STUDY: has been to evaluate the potential role of RCAS1 protein in creating the suppressive tumor microenvironment in pharyngeal squamous cell carcinomas. The immunoreactivity of RCAS1, CD3, CD25, CD68, CD69 and Foxp3 was assessed in the tissue samples of the tumor, in tumor microenvironment and in the reference samples of palatine tonsils in chronic inflammation. RESULTS: A statistically significantly higher RCAS1 antigen immunoreactivity was identified in pharyngeal cancer samples than in the stromal samples, the presence of RCAS1 positive macrophages infiltrating the tumor and its stroma was also noticed. The statistically significantly higher RCAS1 antigen immunoreactivity level was identified in the pharyngeal cancer samples in patients with the presence of lymph node metastases in comparison to patients without metastases. The infiltration of CD68 positive cells (macrophages) was significantly higher in the stromal tissue samples than in cancer samples and it was in both, the tumor and the stroma, significantly higher in patients with the presence of lymph node metastases than in patients without metastases. Additionally the presence of CD3 positive TILs was noticed in the tissue of the tumor and in its stroma, the cells were activated, typified by CD69 immunoreactivity which was higher than in the reference samples, and impaired cytotoxicity with low CD25 antigen immunoreactivity. This observation confirmed the presence of selective immune suppression within the tumor and the stroma. CONCLUSION: RCAS1, an active factor secreted by the tumor and present in its stroma may play an important role in the phenomenon of tumor escape from host immunological surveillance and in creating the immune tolerance for the tumor cells, as well as in the tumor microenvironment remodeling with creating its suppressive profile enabling the further tumor growth and metastases.

The impact of lower induction values of 50 Hz external electromagnetic fields on in vitro T lymphocyte adherence capabilities.

Our research thus far has concerned the impact of external electromagnetic fields (50 Hz) and low (0.01-10 mT) induction on adherence capabilities of T lymphocytes obtained from the blood of patients with head and neck tumors. We know that the in vitro adherence capability of T lymphocytes towards surfaces in cancer patients is less than that of control. Previously, we have found that exposure to electromagnetic fields (50 Hz/0.01-10 mT) increases the capability of T lymphocytes, in larynx/pharynx cancer patients, to adhere in vitro to surfaces, achieving almost physiological values, in not only pre-treatment patients but also those receiving treatment in the course of follow-up. The capability of T lymphocytes in controls (voluntary blood donors) to adhere to surfaces was also increased (50 Hz/0.01-0.5 mT). The present study concentrates on the significance of the level of electromagnetic field induction in order to determine whether low induction values can restore T lymphocytes adherence capabilities. Testing a subset of 20 patients showed a statistically significant difference (p<0.05) in the in vitro adherence capacity of T lymphocytes between both 0.01 and 0.05, and 0.1 mT induction levels. In the control group (patients diagnosed with chronic sensorineural hearing loss) there was even a statistically significant difference between induction values of 0.05 and 0.01 mT. A statistically significant difference (p<0.05) was also achieved with induction levels of 1 and 10 mT compared to 0.5, 0.1, and 0.05 mT, respectively. Therefore, we concluded that lower induction values resulted in a more biologically significant response.

[Analysis of serum T-lymphocyte subsets and NK cell activity in patients with squamous cell carcinoma of pharynx and larynx].

OBJECTIVE: To investigate the alteration of T-lymphocyte subsets and NK activity in patients with squamous cell carcinoma of pharynx and larynx. METHOD: T-lymphocyte subsets and NK activity were determined by flow cytometry in 123 patients with squamous cell carcinoma of pharynx and larynx. Blood samples of 36 nontumor patients were used as control. RESULT: The total T lymphocytes were lower in patients with squamous cell carcinoma of pharynx and larynx than control group significantly (P < 0.05). The levels of helper lymphocyte subsets were little lower than those in control group(P > 0.05). On the other hand, the levels of suppressor lymphocytes in patients were higher than those in the control group (P < 0.05). Therefore, the CD4/CD8 ratios in patients were lower than those of the control group statistically (P < 0.05). There was no statistical difference in activated T lymphocytes and total B lymphocytes (P > 0.05), but NK activity in patients were lower than those in control group significantly (P < 0.01). There was no statistical difference in total T lymphocytes between stage I-II and stage III--IV (P > 0.05). The levels of helper lymphocyte subsets in stage I-II patients were little higher than in stage III-IV patients (P > 0.05), but the levels of suppressor lymphocytes in stage I-II patients were lower than in stage III-IV patients (P < 0.01). The CD4/CD8 ratios in stage I-II patients were significantly higher than in stage III-IV patients (P < 0.01). The levels of total B lymphocytes in stage I-II patients were significantly higher than in stage III-IV patients (P < 0.05). The activated T lymphocytes and NK activity did not changed statistically (P > 0.05). CONCLUSION: The immune function in patients with squamous cell carcinoma of pharynx and larynx is disordered and lower. With advanced stage disease, not only the cellular immune function in patients decrease gradually, but also the humoral immunity is lower. Analyzing T-lymphocyte subsets and NK activity determined by flow cytometry would be easy and helpful to evaluate the immunologic condition of every patient.

Distribution of immune cells in head and neck cancer: CD8+ T-cells and CD20+ B-cells in metastatic lymph nodes are associated with favourable outcome in patients with oro- and hypopharyngeal carcinoma.

BACKGROUND: Tumour infiltrating lymphocytes (TIL) are generally considered to represent a host immune response directed against tumour antigens. TIL are also increasingly recognised as possible prognostic parameters. However, the effects observed are variable indicating that results cannot be extrapolated from type of tumour to another. Moreover, it has been suggested that primary solid tumours may be ignored by the immune system and that a meaningful immune response is only mounted in regional lymph nodes. METHODS: We have examined the local distribution of immune cells in tumour-related compartments in head and neck squamous cell carcinomas (HNSCC). In a second step, the prognostic impact of these cells on disease-free survival (DFS) was analysed. A total of 198 tissue cores from 33 patients were evaluated using tissue mircroarray technique and immunohistochemistry. Tumour-infiltrating immune cells were identified using antibodies specific for CD3, CD8, GranzymeB, FoxP3, CD20 and CD68 and quantified using an image analysis system. RESULTS: We demonstrate a relative expansion of FoxP3+ regulatory T-cells (Treg) and of cytotoxic T-cells among tumour infiltrating T-cells. We also show that intratumoural CD20+ B-cells are significantly more frequent in metastatic deposits than in primary tumours. Furthermore, we observed a reduced number of peritumoural CD8+ T-cells in metastatic lymph nodes as compared to univolved regional nodes suggesting a local down-modulation of cellular immunity. All other immune cells did not show significant alterations in distribution. We did not observe an association of tumour infiltrating immune cells at the primary site with outcome. However, increased numbers of intraepithelial CD8+ TIL in metastatic tumours as well as large numbers of peritumoural B-cells in lymph node metastases were associated with favourable outcome. Unexpectedly, no effect on patient outcome was observed for Treg in any compartment. CONCLUSION: Our results suggest that alterations in lymphocyte distribution in regional lymph nodes rather than at the primary tumour site may be relevant for patient prognosis. Moreover, we demonstrate that in addition to cellular immunity humoral immune responses may be clinically relevant in anti-tumour immunity.

The association between RCAS1 expression in laryngeal and pharyngeal cancer and its healthy stroma with cancer relapse.

BACKGROUND: The purpose of this study has been to establish the level of RCAS1 - a membrane protein expressed in various cancer cells and able to induce apoptosis of CTLs and NK cells in pharyngeal and laryngeal cancer and its clear surgical margin - with respect to clinicopathological features and to patient's follow up and evaluate its possible role in cancer relapse. METHODS: A total of 122 tissue samples were obtained: 51 samples from laryngeal and pharyngeal squamous cell carcinoma, 51 samples from the clear surgical margins of these tumors, and 20 tissue samples derived from the healthy mucous membranes of the upper respiratory tract mucosa of patients without cancerous tumors. Patients were observed for a total of 4 years following surgical treatment. The level of RCAS1 expression was assessed by immunohistochemistry and Western blot. RESULTS: RCAS1 was identified in all laryngeal and pharyngeal carcinomas and in almost all the clear surgical margin samples. The level of RCAS1 expression was significantly higher in the cancerous samples than in the clear surgical margins and was determined to be related to the grade of the cancer and the presence of lymph node metastases. In cases of cancer relapse, significantly higher levels of RCAS1 expression were observed in the clear surgical margins. CONCLUSION: Selective cytotoxic immune cell suppression concomitant with tumor growth and associated with RCAS1 expression seems to be an important event connected with cancer relapse.

Changes of leukocyte adherence ability under the influence of magnetic field in the course of a treatment of patients with laryngeal and pharyngeal carcinoma.

The authors were monitoring adherence ability of T lymphocytes in vitro in patients with laryngeal and pharyngeal carcinoma at the presence of tumor-specific and viral LDH antigen. The results were assessed and expressed in percent of non adherent T lymphocytes (NAL). First, NAL in patients before initiating the treatment was compared with NAL control group (voluntary blood donors). The ability of the adherence in T lymphocytes in the control group is statistically significantly higher. Further on, NAL in the course of a successful oncological treatment was monitored at the interval of 6 months following the treatment, and further on at yearly intervals. NAL level drops statistically significantly within 6 months and then hold on at levels with no statistical difference unlike the control group, however, the ability of T lymphocyte in patients to adhere remains statistically significantly lower. Statistically significantly higher levels of NAL are at the presence of LDH viral antigen. Further on, the authors were following the influence of magnetic sinusoidal field of power frequency (50 Hz) of a low induction (0.5, 0.1, and 0.05 mT) on NAL. NAL values under the influence of an experimental magnetic field before initiating the treatment as well as in the course of a successful oncological treatment are statistically significantly lower. It means that magnetic filed increases the adherence ability of T lymphocytes in patients with laryngeal and pharyngeal cancer in vitro.

The TAG family of cancer/testis antigens is widely expressed in a variety of malignancies and gives rise to HLA-A2-restricted epitopes.

The TAG-1, TAG-2a, TAG-2b, and TAG-2c cancer/testis genes, known to be expressed in an unusually high percentage of melanoma cell lines, are shown here to be expressed in a variety of tumor lines of diverse histologic type, including cancers of the brain, breast, colon, lung, ovary, pharynx, and tongue. The genes are also expressed in fresh, uncultured melanoma, and ovarian cancer cells. Epitope prediction algorithms were used to identify potential HLA-A1, HLA-A2, HLA-A3, HLA-B7, and HLA-B8 epitopes, and these potential epitopes were tested for their ability to stimulate a peptide-specific cytotoxic T lymphocyte response using lymphocytes from healthy donors. Two HLA-A2-restricted epitopes (SLGWLFLLL and LLLRLECNV) were identified using this approach. Cytotoxic T lymphocytes specific for each of these peptides were capable of recognizing tumor cells expressing both the corresponding class I major histocompatibility complex encoded molecule and the TAG genes. These results indicate that TAG-derived peptides may be good components of a therapeutic vaccine designed to target melanoma and a variety of epithelial cell-derived malignancies.

Solitary fibrous tumor of the parapharyngeal space.

Solitary fibrous tumors are benign neoplasms of mesenchymal origin. They usually arise from the visceral or parietal pleura and peritoneum, although they have been found in many areas throughout the body. We report a case of solitary fibrous tumor of the parapharyngeal space. Microscopically, the tumor contained spindle cells with areas of marked hypercellularity without a definitepattern. Consistent with a benign lesion, there were few mitoses and no necrosis. The tumor cells stained strongly positive for CD34 and vimentin. At the 2-year follow-up, the patient was well and free of local and/or distant disease.

Migration of tumor antigen-pulsed dendritic cells after mucosal administration in the human upper respiratory tract.

Tumor-specific peptide-pulsed dendritic cells (DC) were administered via different routes to a group of patients with head and neck cancers. The migration and homing patterns of such antigen-stimulated cells was carefully studied employing single photon emission computed tomography (SPECT). The DC administered directly into the nasal submucosa quickly migrated very rapidly to the regional neck lymph nodes in the neck. However, after inoculation of the cells into the palatine tonsils, the DCs remained close to the site of administration and did not migrate to the regional lymph nodes or to other mucosal regions. After nasal submucosal administration of the DC, tumor-antigen-specific cytotoxic T cells were detected in the ipsilaterals but not in the contra lateral lymph nodes. These results suggest that after antigen processing, the regional lymph nodes serve as inductive sites for development of mucosal immune responses and for induction of memory cells during the local immunological responses in the nasopharyngeal-associated lymphoid tissue in man.