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Inhibition of lymphocyte function by head and neck carcinoma cell line soluble factors
J W Bailet1, A Lichtenstein, G Chen
1Division of Head and Neck Surgery, Veterans Affairs Medical Center West Los Angeles, USA.
Background:
Immunosuppression in patients with head and neck cancer is well recognized. Previous investigations have demonstrated graded immunosuppression that becomes more pronounced as lymphocyte activity is measured closer to the primary neoplasm. In fresh tumors, a soluble factor has been identified that may partly account for the observed graded immunosuppression.
Objective:
To examine the effect of soluble factors produced by head and neck sqamous cell carcinoma cell lines on the generation of lymphokine activated killer cell cytotoxicity and peripheral blood lymphocyte proliferation induced by interleukin 2, concanavalin A, and phytohemagglutinin.
Design:
Conditioned supernatant fluids were generated in a 4-day incubation period, using 5 head and neck squamous cell carcinoma cell lines, and were assayed for the ability to inhibit the generation of lymphokine activated killer cell cytotoxicity and naive peripheral blood lymphocyte proliferation induced by interleukin 2, concanavalin A, and phytohemagglutinin.
Results:
All conditioned supernatant fluids significantly inhibited the generation of lymphokine activated killer cell cytotoxicity relative to controls, and this inhibition was dose dependent. In contrast, supernatant fluids from a myelogenous leukemic tumor cell line, K562, and an ovarian epithelial cell line, SKOV-3, failed to inhibit cytotoxicity. Supernatant fluids conditioned with head and neck squamous cell carcinoma cell lines also profoundly inhibited the naive peripheral blood lymphocyte proliferation induced by interleukin 2, concanavalin A, and phytohemagglutinin.
Conclusions:
These studies demonstrate that the cell lines of head and neck squamous cell carcinoma produce soluble factors that inhibit lymphocyte function. Furthermore, these experiments suggest that the inhibition previously observed with enzymatically disaggregated fresh tumors is due to factors produced by the tumor cells rather than by other cells within the tumor matrix.
Insights
Head and neck squamous cell carcinoma cell lines produce soluble factors that suppress immune cell activity. These factors inhibit lymphokine-activated killer cell cytotoxicity and lymphocyte proliferation, indicating a direct tumor cell role in immunosuppression.
Area of Science:
- Immunology
- Oncology
- Cancer Research
Background:
- Immunosuppression is a known characteristic of head and neck cancer.
- Lymphocyte activity decreases closer to the primary tumor.
- Soluble factors in fresh tumors may contribute to this immunosuppression.
Purpose of the Study:
- To investigate the impact of soluble factors from head and neck squamous cell carcinoma (HNSCC) cell lines.
- To assess the effect on lymphokine-activated killer (LAK) cell cytotoxicity generation.
- To evaluate the influence on peripheral blood lymphocyte proliferation.
Main Methods:
- Generated conditioned supernatant fluids from 5 HNSCC cell lines over 4 days.
- Assayed inhibition of LAK cell cytotoxicity.
- Assayed inhibition of lymphocyte proliferation induced by IL-2, ConA, and PHA.
Main Results:
- All HNSCC supernatant fluids significantly inhibited LAK cell cytotoxicity in a dose-dependent manner.
- Supernatants from non-HNSCC cell lines (K562, SKOV-3) did not inhibit cytotoxicity.
- HNSCC supernatants profoundly inhibited IL-2, ConA, and PHA-induced lymphocyte proliferation.
Conclusions:
- HNSCC cell lines secrete soluble factors that inhibit key lymphocyte functions.
- These findings suggest tumor cells, not other tumor matrix cells, are the source of immunosuppressive factors.
- This supports the hypothesis that direct tumor cell production mediates immunosuppression in head and neck cancer.