Interleukin-2 production in head and neck cancer patients

Hargett, Steven; Wanebo, Harold J.; Pace, Ronald C.; Katz, Daniel; Sando, Julianne J.; Cantrell, Robert W.

doi:10.1016/0002-9610(85)90153-9

Cited by 18 publications

(6 citation statements)

References 14 publications

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“…Depressed IL-2 production by peripheral blood lymphocytes has been noted in patients with head and heck cancer [15], gliomas [10], and a variety of other cancers [54], as well as in tumor-bearing rats [44]. Depressed IL-2 production could also contribute to defects in natural killer (NK) cell and macrophage activity, as both these cell types are responsive to IL-2 [18,53].…”

Section: Discussionmentioning

confidence: 99%

Inhibition of interleukin-2 production by tumor cell products and by CKS-17, a synthetic retroviral envelope peptide

Nelson

1990

Cancer Immunol Immunother

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Tumor cells of all types and species tested have been found to produce, in culture, substances that depress the expression of cell-mediated immunity, in the form of delayed-type hypersensitivity reactions in mouse feet. The factors responsible appear related immunologically to the retroviral envelope protein p15E. We have measured the effects of tumor products and conjugates of a p15E-related peptide, CKS-17, on interleukin-2 (IL-2) production by cultured, mitogen-stimulated EL4 cells; in this system IL-2 production is independent of IL-1. Supernatants of cultures of mouse, human and guinea-pig tumor cells inhibited IL-2 production in a dose-dependent fashion. CKS-17 conjugates, but not control conjugates, also inhibited IL-2 production. Responses to IL-2 of the CTLL line used were less inhibited by tumor products and very slightly inhibited by CKS-17 conjugates. IL-2 receptor density, assayed by flow cytometry, was not inhibited. IL-2 production was inhibited whether the tumor products or CKS-17 conjugates were added early or late in the course of culture of stimulated EL4 cells. Inhibition by CKS-17 conjugates was selective in that IL-2 production was inhibited to a greater degree than general protein synthesis in EL4 cells, and general protein synthesis by fibroblasts was unaffected. Measurement of IL-2 mRNA suggested that inhibition of IL-2 production was mediated post-transcriptionally. Fractionation of six different tumor supernatants on Sephacryl S-300 revealed a single peak of activity with an apparent molecular mass of 18 kDa. Antibodies to CKS-17 conjugates neutralized the inhibitory effect of native tumor products on IL-2 production. Inhibition of IL-2 production, by factors related to p15E, provides a strategically effective means of subversion of host defenses by tumors, and abrogation of this inhibition by means of antibodies might promote host resistance to tumor growth.

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Section: Discussionmentioning

confidence: 99%

Inhibition of interleukin-2 production by tumor cell products and by CKS-17, a synthetic retroviral envelope peptide

Nelson

1990

Cancer Immunol Immunother

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“…PBL are the least immunosuppressed population of effector cells. Early in the disease process, PBL respond normally to mitogens such as phytohemagglutinin (PHA), concanavalin A (Con A), or other stimuli, whereas with progression of cancer, these responses deteriorate 72,78–87 . Patients with early stage HNSCC have normal T‐cell counts and CD4:CD8 ratios in their peripheral blood, whereas patients with advanced disease have reduced counts, decreased numbers of CD4+ cells, and small reductions in CD8+ cells 77,78,88–94 …”

Section: Discussionmentioning

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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“…Higher incidence of oral cancer in India has been generally attributed to the common habit of chewing betel leaf with areca nut and tobacco (2). Reports from other laboratories (3)(4)(5)(6)(7)(8)(9) and those of ours (10)(11)(12) indicate depression in some aspects of cell mediated immune responses in patients with head and neck cancer, and oral cancer.…”

mentioning

confidence: 53%

“…Regulatory role of IL-2 in depressed T cell responses is well documented in patients with SCC of head and neck, and of oral cavity (3)(4)(5)(6)22). Most of these studies are directed to responses of circulating T cells.…”

Section: Discussionmentioning

confidence: 99%

lnterleukin‐2 mediated regulation of mitogen‐activated T cell reactivity from different lymphoid sources in patients with squamous cell carcinoma of the oral cavity

Murali¹,

Somasundaram²,

Rao

et al. 1989

J Oral Pathology Medicine

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Peripheral blood lymphocytes (PBL) from patients with oral cancer (treated and untreated), oral leukoplakia and healthy donors; lymphocytes from metastatic and non-metastatic lymph nodes (met LNL and non-met LNL); and tumor infiltrating lymphocytes (TIL) were tested for proliferative response to mitogen PHA (phytohemagglutinin) and its augmentation by recombinant Interleukin-2 (rIL-2), for expression of Tac antigen (CD25) and for production of IL-2. Depressed PHA responses were found in PBL of treated and untreated patients, and in TIL. Addition of IL-2 could bring about 16% to 31% augmentation in lymphocyte response to PHA from all the three sources. PBL from 50% of healthy donors, 45% of patients with leukoplakia, 25% untreated oral cancer patients and 35% treated oral cancer patients showed IL-2 mediated augmentation of PHA response. While, 40% non-met LNL samples, 70% met LNL samples and only 23% TIL samples showed increased mitogen induced proliferation by IL-2. The augmented levels of PHA response of PBL from treated and untreated patients, and of TIL, were still below those of normal PBL. PBL from patients with leukoplakia, treated oral cancer patients and TIL showed depressed CD25 antigen expression. Depressed IL-2 production was observed only in PBL of leukoplakia patients. Thus the IL-2 mediated events of T cell activation from different lymphoid sources in patients with oral cancer did not correlate with their proliferative responses.

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Interleukin-2 production in head and neck cancer patients

Cited by 18 publications

References 14 publications

Inhibition of interleukin-2 production by tumor cell products and by CKS-17, a synthetic retroviral envelope peptide

Inhibition of interleukin-2 production by tumor cell products and by CKS-17, a synthetic retroviral envelope peptide

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

lnterleukin‐2 mediated regulation of mitogen‐activated T cell reactivity from different lymphoid sources in patients with squamous cell carcinoma of the oral cavity

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