Abstract

Immune cells and cytolytic activity within the tumor microenvironment are being intensively studied. Through transcriptome profiling, immune cell enumeration using the xCell tool and cytolytic activity quantification according to granzyme A (GZMA) and perforin (PRF1) mRNA levels, we investigated immunoreactivity in tumor and/or tumor‐free tongue tissue samples from 31 patients with squamous cell carcinoma of the oral tongue and 14 healthy individuals (control tongue tissues). We found significantly altered immune cell compositions (p < 0.001) and elevated cytolytic activity (p < 0.001) in tumor compared to tumor‐free samples, and altered infiltration of a subset of immune cells (e.g. CD8+ T cells, p < 0.01) as well as increased cytolytic activity (p < 0.001) in tumor‐free compared to control samples. Controlling for patient age at diagnosis and tumor stage, Cox regression analysis showed that high cytolytic activity in tumor‐free samples associated with improved disease‐free survival (hazard ratio= 4.20, 95% CI = 1.09–16.20, p = 0.037). However, the degree of cytolytic activity in tumor samples did not provide prognostic information. Taken together, our results show the presence of cancer‐related immune responses in clinically tumor‐free tongue in patients with squamous cell carcinoma of the oral tongue. Measuring cytolytic activity in tumor‐free tongue samples contralateral to tumor might thus be an effective approach to predict clinical outcome.

Highlights

  • The cancer immune microenvironment has been intensively studied in the past few decades, paving the way for the recent clinical application of immunotherapies targeting immune checkpoints such as cytotoxic T-lymphocyte associated protein 4 (CTLA4), programmed cell death 1 (PDCD1/PD1), and programmed cell death 1 ligand 1 (CD274/PDL1) [1,2]

  • We show altered immune infiltration and increased cytolytic activity in tumor samples and in clinically tumor-free tongue samples from patients with Squamous cell carcinoma of the oral tongue (SCCOT) compared to normal tongue from healthy individuals

  • There was no significant difference in age, sex, tumor size and stage between high or low score groups (Table 3); within the survival data for high cytolytic activity patients, we found that the three patients who had died within 3 months were all 78 years or older

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Summary

Introduction

The cancer immune microenvironment has been intensively studied in the past few decades, paving the way for the recent clinical application of immunotherapies targeting immune checkpoints such as cytotoxic T-lymphocyte associated protein 4 (CTLA4), programmed cell death 1 (PDCD1/PD1), and programmed cell death 1 ligand 1 (CD274/PDL1) [1,2]. Various immunogenomic approaches have been applied to dissect tumor-immune cell interactions [3,4] and accumulating evidence supports the impact of host immunity on cancer progression and response to immunotherapy [4,5,6,7,8]. A novel gene signature-based method called xCell was developed, identifying 64 immune and stromal cell types [10]. By integrating the advantages of gene set enrichment with deconvolution, xCell provides a comprehensive perspective on the cellular heterogeneity of tissues [10,11]

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