We have reported earlier that PBMC isolated from immunosuppressed HNSCC patients appear immunoefficient after in vitro
stimulation of these cells with IFNα2b4
. Mechanism to overcome the immunosuppression was also elucidated17,18
In this preliminary study, the detailed haematological and immune functions of patients with TSCC were assessed and all patients exhibited poor immune functions in terms of the poor cytotoxic function of PBMC, less number of cytotoxic T and NK cells and type1/type2 cytokine imbalance. These immunocompromised patients appeared more immunologically unstable, when immune parameters were examined after cisplatin+5-FU therapy. Patients at this point were immunocompromised with leukepenia and low platelet count. In spite of the efficacy of cisplatin+5-FU treatment in lowering tumour burden of HNSCC patients, it is often associated with immune paralysis19
. Following cisplatin+5-FU treatment, IFNα2b therapy was initiated and patients were examined clinically and immunologically upon completion of the treatment. The study revealed a prominent recovery in the haematological and immunological functions.
Based on clinical examination, these seven TSCC patients were categorized into three groups. Two patients responded completely and their survival was recorded 28 months after initiation of the treatment. Robust immunostimulation by IFNα2b was demonstrated in these two patients, particularly in patient no. 3. This particular patients reported in clinic as tumor free and clinically fit 50 months after treatment initiation. Four patients with partial clinical response also demonstrated immune response following IFNα2b therapy and no difference was noted between patients with CR and PR. Improved prognosis and prolonged survival of head and neck cancer patients using different chemotherapeutic regimens, along with IFNα2b was reported from an initial multicentre open trial15
, however, no effort was done to know the immune status of these patients. Volck et al16
treated 14 patients of recurrent HNSCC and reported clinical benefit, including complete response in one. They checked the NK cell activity of these patients and observed a superior correlation of NK cell function with clinical outcome. We also found enhancement of the NK cell activity and NK derived cytokine milieu after IFNα2b therapy. Frequency of T cells and their cytotoxic ability was also increased after IFNα2b treatment. It was noted that proportion of CD8+
cells decreased after chemotherapy, but was increased after completion of chemo-immunotherapy. In most of the cases these values exceeds the CD8 values observed in pre-treatment conditions. Increase in CD4/CD8 ratio following IFNα2b treatment indicated favourable prognosis of these patients. Shah et al20
reported that in cancer cervix patients, survival rate was significantly higher in patients with a high CD4/CD8 ratio as compared to patients who had a low CD4/CD8 ratio. Unitt et al21
observed that a high CD4/CD8 ratio was associated with a reduced risk of tumour recurrance after liver transplantation in hepatocellular carcinoma. IFNα2b activated T cells can kill cancer cells, possibly by the induction of cytotoxic T lymphocyte (CTL) response and antibody dependent cellular cytotoxicity (ADCC). IFNα2b mediated upregulation of the perforin, granzymeB synthesis and expression was associated with either antibody or CTL mediated tumour cell killing17
. Patients with CR were able to maintain the immune system in activated state, till the completion of radiotherapy, 20 days after the completion of the IFNα2b therapy. Such durable immune activation was not demonstrated in patients with PR or NR.
Neoadjuvant chemotherapy with platinum and taxens or concomitant chemo-radiotherapy in advanced inoperable TSCC patients is a usual clinical practice. Results obtained from this preliminary study with cisplatin+5-FU followed by IFNα2b suggest that inclusion of IFNα2b in the therapeutic protocol enhances the immune response of immunosuppressed patients, that may ultimately enhance the clinical outcome. No mucositis was experienced in any patient after IFNα2b therapy possibly due to the use of IFNα2b for a short duration (3 wk). Leukepenia and neutropenia were monitored on a regular basis and controlled by the use of GCSF as and when required. Similar studies with large number of TSCC patients are required to be conducted, where repeated IFNα2b therapy can be given to maintain long term immune activation and concomitant radiotherapy can be tested.