A natural cytokine mixture (IRX-2) and interference with immune suppression induce immune mobilization and regression of head and neck cancer

Verástegui, Emma; Barrera, José Luís; Zinser, Juan W; Rio, Roxana del; Meneses, Abelardo; Garza, Jaime de la; Hadden, John W.

doi:10.1016/s0192-0561(97)00059-3

Cited by 21 publications

(16 citation statements)

References 27 publications

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“…Although one study showed that perilymphatic IL-2 injection did not change the number of T-cells in peripheral blood and restore suppressed immune function [5], another group showed that regional perilymphatic injections of a mixture of cytokines significantly increased the total lymphocyte counts, CD3 + T-cells, CD4 + T-cells, and CD8 + T-cells. The overall lymphocytic infiltration increased 4.7 fold [6]. Guided by a similar philosophy of promoting the proliferation of effector immune cells, tumor vaccine clinical trials were later developed to increase the specificity and intensity of anti-tumor immune response.…”

Section: Does the Number Of T-cells In The Tumor Microenvironment Matmentioning

confidence: 99%

Telltale tumor infiltrating lymphocytes (TIL) in oral, head & neck cancer

et al. 2016

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Evidence gleaned from recent studies on the role of tumor-infiltrating lymphocytes (TILs) suggests that cancer is not only a genetic disease but also an immunologic disease. Head and Neck Squamous Cell Carcinoma (HNSCC) has been a significant model to study cancer cell-immune cell interactions. First, immune cell infiltration is an important feature of these tumors. Second, HNSCC frequently develops resistance to immunogenic cytotoxicity, which provides a window to decipher how tumors engage the immune system to establish immune tolerance. Finally, chemoradiation therapy, as a central modality for HNSCC treatment, has been shown to elicit immune activation. The presence of effector immune cells in the tumor microenvironment is often associated with superior clinical response to adjuvant therapy. On the other hand, an activated immune system, in addition to limiting tumor initiation and progression, could also exert selective pressure to promote the growth of less immunogenic tumors, as a pivotal immunoediting process. But it remains unclear how cancer cell signaling regulates tumor immunogenicity and how to mitigate HNSCC-potentiated TIL suppression. In this review, we will revisit the prognostic role of TILs in HNSCC, and collectively discuss how cancer cell machinery impacts upon the plasticity of TILs.

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Section: Does the Number Of T-cells In The Tumor Microenvironment Matmentioning

confidence: 99%

Telltale tumor infiltrating lymphocytes (TIL) in oral, head & neck cancer

et al. 2016

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“…Immunotherapy using cytokines started in the 1980s and continues to be evaluated for the treatment of cancer; it has met with only limited success in HNSCC. IL‐2 and interferon (IFN)‐α were the first cytokines tested in HNSCC 12,13,17,19,20,27–35 . A preliminary trial of nonrecombinant IFN‐α in patients with HNSCC was performed by Vlock and colleagues, 27 which demonstrated tolerable toxicity and potential anti‐tumor activity.…”

Section: Introductionmentioning

confidence: 99%

“…Another cytokine, IFN‐γ, which also up‐regulates cell‐mediated immunity, has shown early clinical promise but has not been studied extensively in clinical trials 31 . In a series of small trials, Hadden et al 32–34 administered natural mixtures of cytokines (IRX‐2) peritumorally into patients with advanced HNSCC before surgery. Clinical and pathologic findings indicated that tumor regression was observed in several cases and was mediated by activated lymphocytes accumulating at the tumor site 33,34 .…”

Section: Introductionmentioning

confidence: 99%

Covalent linking of proteins and cytokines to suture: Enhancing the immune response of head and neck cancer patients

et al. 2003

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Backgrwund:The immune system of advanced stage head and neck cancer patients is frequently suppressed. Poor immune function has been correlated with poor clinical outcome. Immunotherapeutic strategies have been previously attempted in an effort to enhance immune function and improve survival. Previous studies have shown surgical suture can be transformed into an immune stimulant capable of activating the T lymphocytes of cancer patients. The development of a process for covalently linking proteins and cytokines to suture could have enormous potential for the in vivo manipulation of the immune system. Hypothesis: We hypothesize proteins and cytokines can be covalently linked to surgical suture while preserving their functional properties. Study Design: Prospective study testing normal donor and head and neck squamous cell carcinoma (HNSCC) patient lymphocytes. Method. Polyester suture was acid hydrolyzed followed by reacting with l-ethyl-3(-3-dimethylamino propyl carbodiimide) (EDAC) to create a suture-EDAC intermediate. activity. The optimal conditions for linking 1C2 or m-7 were defined. The covalently linked cytokines retained their immune enhancing properties for stimulating PBL and lymph node lymphocytes (LNL) from HNSCC patients to proliferate, generate a TH1 immunologic profile of cytokines (IG2, IL-12, IFN-y), and stimulate T lymphocytes. Conclusion: This is the first report to demonstrate that cytokines can be covalently linked to surgical sutures and retain their immune-stimulating properties. Proteins linked to suture also retained their enzymatic activity. The clinical implications of functionally active cytokines or proteins linked to surgical suture may be very significant in the future for manipulating the immune system in vivo o r enhancing wound healing.

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“…In the past, in head and neck cancer, interleukin‐based cytokine therapy produced some immuno‐augmenting results. 4–10 For example, in a series of clinical studies, recombinant human interleukin‐2 was successfully used to improve immune function of patients with head and neck cancer (as measured by cytotoxic T lymphocyte and delayed type hypersensitivity responses). In vivo administration of recombinant IL‐2 induced in various trials increased density of CD25‐positve cells as well as natural killer (NK) cells, human leukocyte antigen‐DR‐positive lymphocytes, and T cells; however, data on the efficacy of the clinical responses are not available yet.…”

Section: Introductionmentioning

confidence: 99%

“…In several of these studies, positive clinical responses have been observed when the cytokine mixture was administered perilymphatically or peritumorally. 8–10 Analysis of the mononuclear infiltrate in head and neck cancer treated with the cytokine mixture demonstrated that treated tumors were richer in T cells 11 or T and B cells 12 and that this correlated with increased response to definitive follow‐up treatment (surgery followed by radiation therapy) and reduction in recurrence rate.…”

Section: Introductionmentioning

confidence: 99%

The Effect of Leukocyte Interleukin Injection (Multikine®) Treatment on the Peritumoral and Intratumoral Subpopulation of Mononuclear Cells and on Tumor Epithelia: A Possible New Approach to Augmenting Sensitivity to Radiation Therapy and Chemotherapy in Oral Cancer—A Multicenter Phase I/II Clinical Trial

et al. 2003

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The results could be highly beneficial for patients with oral squamous cell carcinoma. First, leukocyte interleukin injection treatment induces T-cell migration into cancer nests and, second, noncycling cancer cells may enter cell cycling on administration of leukocyte interleukin injection. This latter effect may modulate the susceptibility of cancer cells to radiation therapy and chemotherapy. The findings may indicate a need to re-evaluate the way in which follow-up treatment (with radiation therapy and chemotherapy) of patients with head and neck cancer is currently approached.

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A natural cytokine mixture (IRX-2) and interference with immune suppression induce immune mobilization and regression of head and neck cancer

Cited by 21 publications

References 27 publications

Telltale tumor infiltrating lymphocytes (TIL) in oral, head & neck cancer

Telltale tumor infiltrating lymphocytes (TIL) in oral, head & neck cancer

Covalent linking of proteins and cytokines to suture: Enhancing the immune response of head and neck cancer patients

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