Immunobiology of head and neck cancer

Abstract

The development of head and neck cancer (HNC) is strongly influenced by the host immune system. Recent evidence for the presence of functional defects and for apoptosis of tumor-infiltrating as well as circulating T cells in patients with HNC emphasizes the fact that their antitumor responses are compromised. It appears that H&N tumors not only effectively escape from the host immune system but also actively corrupt the host antitumor response via several distinct mechanisms. Strategies for restoring immune competence of patients with HNC and for preventing tumor escape are necessary for more effective control of tumor progression. New immunotherapeutic approaches include cytokine-based and DC-based vaccines which are aimed at the restoration of tumor-specific responses and at the protection of immune cells from tumor-induced apoptosis.

Immune response to vaccination with DNA-hsp65 in a phase I clinical trial with head and neck cancer patients

“…23 Another caveat in interpreting our results is the immunosuppression that is characteristic of patients with advanced stages of head and neck cancer. 24 Although this may be a general characteristic of such patients, at least some of the subjects included in this study showed evidence of immune activity, including positive response to skin tests (7 of 21 patients) and high unstimulated lymphoproliferation (41000 c.p.m. ; 8 of 11 patients) ( Table 2 and clinical trial paper 8 ).…”

“…7 However, the use of the intratumoral route is complicated by the highly immunosuppressive microenvironment of the head and neck tumor. 24 Further studies must be conducted to determine whether presentation of tumor antigens by Hsp65 is required for its antitumoral effects or whether these effects are mediated by a reversion of immunosuppression mediated by the proinflammatory properties of this protein. If the latter is true, immunization away from the tumor (for example, skin at a distant site) may prove more efficient in achieving tumor regression by averting the effects of local immunosuppression.…”

CD4+ T helper responses in squamous cell carcinoma of the head and neck

“…5,16,17 On the other hand, tumors escape from immune surveillance by mechanisms such as down-modulation of HLA expression, mutation of these and other tumor antigens, the lack of costimulatory factors, production of immunosuppressive cytokines and apoptosis of effector T cells. 6 To generate tumor-specific T cells from PBMCs or TILs of patients with cancer, permanent tumor cell lines are usually established from tumor specimens. In general, tumor specimens from head and neck regions are difficult to propagate, and they are more often contaminated by bacteria, viruses, and mycoplasma due to their location, compared with the tumors from other locations.…”

“…Gun-1 cells were incubated with IFN-γ (100 IU/ml) for 48 h before being used as stimulators. Autologous MLTC was performed as follows: 2×10 6 PBMCs were stimulated with 2×10 5 MMC (kindly provided by Kyowa Hakko, Tokyo, Japan)-treated Gun-1 cells (100 µg/ml for 30 min at 37 °C). The cells were suspended in 2 ml AIM-V medium supplemented with 10% (v/v) heat-inactivated human AB serum, 20 IU/ml of IL-2 (kindly provided by Shionogi & Co., Ltd. Osaka, Japan), and 25 IU/ml of IL-4 (kindly provided by Ono Pharmaceutical Co., Ltd. Osaka, Japan).…”

“…For example, the production of immunosuppressive factors such as transforming growth factor-β (TGF-β), interleukin (IL)-10, or prostaglandin E-2 (PGE-2) and low levels or lack of expression of tumor antigens, major histocompatibility complex (MHC) molecules, or costimulatory molecules are some of the mechanisms facilitating tumor escape. 6 Therefore, it is not surprising that strong activation signals are necessary to induce and detect autologous tumor-specific T-cell responses in PBLs and TILs of patients with SCCHN.…”