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Immunologic effector cells in head and neck cancer
D Vitolo1, E M Letessier, J T Johnson
1Department of Pathology, University of Pittsburgh School of Medicine, Pa.
Insights
Tumor-infiltrating lymphocytes (TIL) and lymph node lymphocytes (LNL) in head and neck cancer (HNC) patients show impaired cytokine production. LNL near tumors express cytokine mRNA, unlike those further away, suggesting localized immune suppression.
Area of Science:
- Immunology
- Oncology
- Molecular Biology
Background:
- Tumor-infiltrating lymphocytes (TIL) and lymph node lymphocytes (LNL) in head and neck cancer (HNC) patients often exhibit reduced functional responses.
- Impaired cytokine production by these lymphocytes may contribute to their functional incompetence.
Purpose of the Study:
- To investigate the spontaneous and induced production of key cytokines (IL-2, IL-1β, TNF-α, IFN-γ) by TIL, LNL, and peripheral blood lymphocytes (PBL) in HNC patients.
- To determine the in situ expression of cytokine mRNA and IL-2 receptor components in tumor tissues and lymph nodes.
Main Methods:
- Measurement of cytokine production by TIL, LNL, and PBL.
- In situ hybridization to detect cytokine and IL-2 receptor mRNA in tumor tissues and lymph nodes.
- Analysis of lymphocytes from tumor-involved and tumor-free lymph nodes.
Main Results:
- TIL and PBL produced IL-1β and TNF-α, while LNL did not produce measurable levels of these cytokines.
- LNL produced lower levels of IFN-γ compared to PBL.
- TIL and LNL near the tumor expressed mRNA for IL-2, IFN-γ, IL-1β, TNF-α, and IL-2 receptor chains.
- LNL adjacent to the tumor expressed TGF-β mRNA, whereas LNL distant from the tumor did not.
Conclusions:
- Lymphocytes in the tumor microenvironment of HNC patients exhibit distinct cytokine expression profiles.
- LNL near the tumor are activated and express immunosuppressive factors like TGF-β, potentially contributing to local immune evasion.
- Functional impairment of lymphocytes in HNC may be linked to the tumor microenvironment's influence on cytokine production.
Abstract:
Freshly isolated tumor-infiltrating lymphocytes (TIL) and lymph node lymphocytes (LNL) in patients with head and neck cancer (HNC) often have low or undetectable functional responses. Because impaired ability of these cells to produce cytokines could be responsible for their functional incompetence, spontaneous and in vitro-induced production of interleukin-2 (IL2), interleukin-1 beta (IL-1 beta), tumor necrosis factor-alpha (TNF-alpha), and interferon gamma (IFN-gamma) by TIL, LNL from tumor-free as well as tumor-involved lymph nodes (LN), and peripheral blood lymphocytes (PBL) were measured. Although TIL or PBL of patients with HNC produced IL-1 beta and TNF-alpha spontaneously or after in vitro activation, LNL did not produce measurable levels of these cytokines. LNL also produced lower levels of IFN-gamma than PBL. In situ hybridization for cytokine mRNA performed with tumor tissues, and LN of patients with HNC showed that TIL as well as LNL localized in the immediate proximity of the tumor were activated, as evidenced by the expression of mRNA for IL2, IFN-gamma, IL-1 beta, TNF-alpha, and both alpha- and beta-chains of the IL2 receptor. In addition, many LNL located next to the tumor expressed mRNA for transforming growth factor-beta (TGF-beta). In contrast, LNL not adjacent to the tumor in involved LN, as well as those in tumor-uninvolved LN, did not express mRNA for cytokines or IL2 receptor.(ABSTRACT TRUNCATED AT 250 WORDS)