Effect of BCG stimulus on proinflammatory cytokine production in laryngeal cancer

Conti-Freitas, Luiz Carlos; Foss‐Freitas, Maria Cristina; Mamede, Rui Celso Martins; Foss, Norma Tiraboschi

doi:10.1007/s00262-008-0520-7

Cited by 8 publications

(5 citation statements)

References 19 publications

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“…Additionally, increased production of TNF-α by PBMC from MB patients was observed in the presence of LPS after the application of BCG-id ( P = 0.017), suggesting a nonspecific immune stimulatory action of BCG on the innate immunity response 30. This is a very interesting response in multibacillary leprosy, where TNF-α acts by inducing macrophage activation, thus favoring destruction of the parasite and the maintenance of IFN-γ production 31.…”

Section: Discussionmentioning

confidence: 98%

Clinical and immunological evaluation after BCG-id vaccine in leprosy patients in a 5-year follow-up study

Zenha¹,

Wambier²,

Novelino³

et al. 2012

JIR

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IntroductionThe use of bacillus Calmette–Guérin (BCG) has long been considered a stimulus for immune reactivity in leprosy household contacts. Probably, the combination of multidrug therapy with BCG could facilitate the clearance of leprosy bacilli in the host, reduce relapse rates, and shorten the duration of skin-smear positivity.MethodsTo investigate the mechanism of action of BCG, a study involving 19 leprosy patients, eleven multibacillary (MB) and eight paucibacillary, was performed to assess the in vitro production of interleukin (IL)-10, interferon (IFN)-γ, tumor necrosis factor (TNF)-α, IL-6, and IL-17 in the supernatant of peripheral blood mononuclear cells, before and 30 days after inoculation with BCG intradermally (BCG-id). Peripheral blood mononuclear cells isolated by Ficoll–Hypaque gradient were cultivated with Concanavalin-A (Con-A), lipopolysccharides (LPS), or BCG. The supernatant was collected for ELISA quantification of cytokines. The immunohistochemistry of IFN-γ, IL-1, IL-10, IL-12, transforming growth factor (TGF)-β, and TNF-α was carried out in biopsies of skin lesions of leprosy patients before and 30 days after inoculation of BCG-id. These patients were followed up for 5 years to assess the therapeutic response to multidrug therapy, the occurrence of leprosy reactions, and the results of bacterial index and anti-PGL-1 serology after the end of treatment.ResultsThe results showed increased production of cytokines after BCG-id administration in MB and paucibacillary leprosy patients. There was statistically higher levels of TNF-α (P = 0.017) in MB patients and of IL-17 (P = 0.008) and IFN-γ (P = 0.037) in paucibacillary patients. Immunohistochemical staining, especially for TNF-α, was more intense in biopsies of MB leprosy patients taken after BCG-id administration, probably for induction of innate human immunity. The clinical evaluation suggests that BCG-id is able to induce a more effective therapeutic response, with reduction of the number and the intensity of leprosy reactions.ConclusionThese results suggest that BCG-id induces activation of the initial phase of immunocellular activity: innate human immunity (increase in TNF-α, IL-12 and macrophage activation). Therefore, we conclude that the use of BCG-id could be indicated as an adjuvant to multidrug therapy in treatment of leprosy patients.

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Section: Discussionmentioning

confidence: 98%

Clinical and immunological evaluation after BCG-id vaccine in leprosy patients in a 5-year follow-up study

Zenha¹,

Wambier²,

Novelino³

et al. 2012

JIR

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“…In a previous study, we evaluated the production of TNF-α and IL-6 in the supernatant of adherent cells cultured from peripheral blood mononuclear cells (PBMCs) isolated from patients with supraglottic laryngeal cancer before and after surgical treatment. We found that BCG is able to modulate the immune response of these patients (6). In this study, we evaluated the production of IFN-γ and IL-10 by cultured PBMCs isolated from patients with advanced supraglottic laryngeal cancer.…”

Section: Introductionmentioning

confidence: 90%

Interferon-gamma and interleukin-10 production by mononuclear cells from patients with advanced head and neck cancer

Conti-Freitas¹,

Foss‐Freitas²,

Mamede³

et al. 2012

Clinics

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OBJECTIVE:This study aims to evaluate the production of interferon-gamma and interleukin-10 by stimulated peripheral blood mononuclear cells isolated from patients with supraglottic laryngeal cancer before and after surgical treatment.METHODS:Fourteen patients with advanced supraglottic laryngeal cancer were studied. Cultures of peripheral blood mononuclear cells isolated during the preoperative and late postoperative periods were stimulated with concanavalin A and Bacille Calmette-Guérin, and the supernatant concentrations of interferon-gamma and interleukin-10 were measured.RESULTS:For non-stimulated cultures, the interferon-gamma levels produced by the preoperative period and the late postoperative period cultures were lower than the levels produced by the control group cultures. The interferon-gamma levels after stimulation with concanavalin A were higher in the late postoperative period cultures than in the preoperative evaluation cultures. Stimulation with Bacille Calmette-Guérin led to the production of similar levels of interferon-gamma and interleukin-10 by all cultures; thus, stimulation increased the levels of interferon-gamma produced by both the preoperative and postoperative cultures relative to the levels produced by the corresponding unstimulated cultures.CONCLUSION:Patients with advanced supraglottic laryngeal cancer exhibit an in vitro deficiency in interferon-gamma secretion by mononuclear cells. Stimulated cells seem to recover this function during the postoperative period.

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“…Several articles have looked at the detailed effect of BCG on cancer cell lines and on human leukocytes in vitro, including two papers using leukocytes from head and neck cancer patients (60)(61)(62)(63). Overall, BCG increased production of most cytokines measured but most notably IL-6, tumor necrosis factor and interferon-gamma, but not IL-2.…”

Section: Bcg As Direct Anticancer Therapy (Alone or In Combination With Existing Treatments)mentioning

confidence: 99%

Repurposing Infectious Diseases Vaccines Against Cancer

et al. 2021

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Vaccines used to prevent infections have long been known to stimulate immune responses to cancer as illustrated by the approval of the Bacillus Calmette–Guérin (BCG) vaccine to treat bladder cancer since the 1970s. The recent approval of immunotherapies has rejuvenated this research area with reports of anti-tumor responses with existing infectious diseases vaccines used as such, either alone or in combination with immune checkpoint inhibitors. Here, we have reviewed and summarized research activities using approved vaccines to treat cancer. Data supporting a cancer therapeutic use was found for 16 vaccines. For 10 (BCG, diphtheria, tetanus, human papillomavirus, influenza, measles, pneumococcus, smallpox, typhoid and varicella-zoster), clinical trials have been conducted or are ongoing. Within the remaining 6, preclinical evidence supports further evaluation of the rotavirus, yellow fever and pertussis vaccine in carefully designed clinical trials. The mechanistic evidence for the cholera vaccine, combined with the observational data in colorectal cancer, is also supportive of clinical translation. There is limited data for the hepatitis B and mumps vaccine (without measles vaccine). Four findings are worth highlighting: the superiority of intravesical typhoid vaccine instillations over BCG in a preclinical bladder cancer model, which is now the subject of a phase I trial; the perioperative use of the influenza vaccine to limit and prevent the natural killer cell dysfunction induced by cancer surgery; objective responses following intratumoral injections of measles vaccine in cutaneous T-cell lymphoma; objective responses induced by human papillomavirus vaccine in cutaneous squamous cell carcinoma. All vaccines are intended to induce or improve an anti-tumor (immune) response. In addition to the biological and immunological mechanisms that vary between vaccines, the mode of administration and sequence with other (immuno-)therapies warrant more attention in future research.

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Effect of BCG stimulus on proinflammatory cytokine production in laryngeal cancer

Abstract: BCG is able to modulate the immune response of patients with advanced supraglottic laryngeal cancer in vitro, increasing the secretion of TNF and IL-6 by macrophages during the postoperative period.

Cited by 8 publications

References 19 publications

Clinical and immunological evaluation after BCG-id vaccine in leprosy patients in a 5-year follow-up study

Clinical and immunological evaluation after BCG-id vaccine in leprosy patients in a 5-year follow-up study

Interferon-gamma and interleukin-10 production by mononuclear cells from patients with advanced head and neck cancer

Repurposing Infectious Diseases Vaccines Against Cancer

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