T-cell exhaustion and stroma senescence – the impact of tumor microenvironment on tumor cell biology and prognosis of head and neck carcinomas

Introduction Immunooncology has gained importance in the treatment of head and neck cancer patients (HNSCC) over the past years and has found its way into the clinical practice of head and neck oncology. Nevertheless, many patients show no or only a transient response to anti-PD1 antibodies, so that further investigations of tumor-immune cell interaction are necessary to expand the spectrum of immunotherapy. In this context, we addressed the relevance of stroma senescence and T cell exhaustion on the prognosis of HNSCC patients in the presented study.

Methods The expression of 5 representative biomarkers indicating stroma senescence and T-cell exhaustion were examined by immunohistochemistry on FFPE tissue samples from a collective of 115 HNSCC patients, evaluated semiquantitatively and correlated with patients' clinical data: PD1, TIM 3, LAG-3, MMP3, and IL-8.

Results There was a significant correlation of increased expression on intra- and peritumoral immune cells with prolonged overall patient survival for the biomarkers TIM 3 (p<0.001) and PD1 (p<0.0101).

Discussion The results of this study demonstrate that the composition and activity of the immunological tumor microenvironment has a significant impact on the prognosis of HNSCC patients. In addition to the already approved anti PD1 antibodies, other immune checkpoints and immune cell populations are promising targets of future immuno-oncological therapeutic approaches aiming at overcoming stroma senescence and T-cell exhaustion.

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Artikel online veröffentlicht:
24. Mai 2022