ABSTRACT
Older adults are at an increased risk of vaccine-preventable diseases partly because of physiologic changes in the immune and other body systems related to age and/or accumulating comorbidities that increase the vulnerability to infections and decrease the response to vaccines. Strategies to improve the response to vaccines include using a higher antigenic dose (such as in the high-dose inactivated influenza vaccines) as well as adding adjuvants (such as MF59 in the adjuvanted inactivated influenza vaccine).
Subject(s)
Influenza Vaccines , Influenza, Human , Vaccine-Preventable Diseases , Aged , Humans , Adjuvants, Immunologic/adverse effects , Influenza Vaccines/adverse effects , Influenza, Human/epidemiology , Influenza, Human/prevention & control , Polysorbates/adverse effects , Squalene/adverse effects , Vaccines, Inactivated/adverse effectsABSTRACT
PURPOSE: Recurrent tumors (RT) of head and neck squamous cell carcinoma (HNSCC) occur in up to 60%, with poor therapeutic response and detrimental prognosis. We hypothesized that HNSCC RTs successfully evade antitumor immune response and aimed to reveal tumor immune microenvironment (TIME) changes of primary tumors (PT) and corresponding RTs. EXPERIMENTAL DESIGN: Tumor-infiltrating leukocytes (TIL) of 300 PTs and 108 RTs from two large independent and clinically well-characterized HNSCC cohorts [discovery cohort (DC), validation cohort (VD)] were compared by IHC. mRNA expression analysis of 730 immune-related genes was performed for 18 PTs and RTs after adjuvant chemoradiotherapy (CRT). The effect of chemotherapy and radiation resistance was assessed with an in vitro spheroid/immunocyte coculture model. RESULTS: TIME analysis revealed overall decrease of TILs with significant loss of CD8+ T cells (DC P = 0.045/VC P < 0.0001) and B lymphocytes (DC P = 0.036/VC P < 0.0001) in RTs compared with PTs in both cohorts. Decrease predominantly occurred in RTs after CRT. Gene expression analysis confirmed loss of TILs (P = 0.0004) and B lymphocytes (P < 0.0001) and showed relative increase of neutrophils (P = 0.018), macrophages (P < 0.0001), dendritic cells (P = 0.0002), and mast cells (P = 0.0057) as well as lower overall expression of immune-related genes (P = 0.018) in RTs after CRT. Genes involved in B-lymphocyte functions and number of tertiary lymphoid structures showed the strongest decrease. SPP1 and MAPK1 were upregulated in vivo and in vitro, indicating their potential suitability as therapeutic targets in CRT resistance. CONCLUSIONS: HNSCC RTs have an immunosuppressive TIME, which is particularly apparent after adjuvant CRT and might substantially contribute to poor therapeutic response and prognosis.
Subject(s)
Carcinoma, Squamous Cell/immunology , Head and Neck Neoplasms/immunology , Lymphocytes, Tumor-Infiltrating/immunology , Tumor Escape/immunology , Tumor Microenvironment/immunology , Aged , CD8-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/metabolism , Carcinoma, Squamous Cell/metabolism , Carcinoma, Squamous Cell/therapy , Cell Line, Tumor , Cell Survival/genetics , Cell Survival/immunology , Cohort Studies , Female , Forkhead Transcription Factors/immunology , Forkhead Transcription Factors/metabolism , Gene Expression Regulation, Neoplastic/immunology , Head and Neck Neoplasms/metabolism , Head and Neck Neoplasms/therapy , Humans , Lymphocytes, Tumor-Infiltrating/metabolism , Male , Middle Aged , Neoplasm Recurrence, Local , Prognosis , Tumor Escape/genetics , Tumor Microenvironment/geneticsABSTRACT
Mycobacterium chimaera, a nontuberculous mycobacterium, is a member of the Mycobacterium avium complex (MAC). This microorganism has recently gained significant notoriety for its association with outbreaks in patients exposed to contaminated heater -cooler devices used during open heart surgeries. We report a case of Mycobacterium chimaera pulmonary infection in a healthcare worker who presented with cough, low grade fever and weight loss with evidence of a lung mass that was initially thought to be a tumor on CT scan imaging. The patient underwent partial left lung lobectomy and pathology revealed necrotizing granulomas with acid fast bacilli and a culture grew M. chimaera. The patient received combination antimycobacterial therapy according to susceptibility results for twelve months with complete resolution of his symptoms and radiographic findings. Infection Control investigation could not find a source of infection in the hospital where he worked during the last ten years. However, the patient rotated in different hospitals before coming to work at this facility and assisted in surgeries in several operating rooms where the heater-cooler devices in question were used.