4.7 Article

Dynamic alterations of circulating T lymphocytes and the clinical response in patients with head and neck squamous cell carcinoma treated with nivolumab

Journal

CANCER IMMUNOLOGY IMMUNOTHERAPY
Volume 71, Issue 4, Pages 851-863

Publisher

SPRINGER
DOI: 10.1007/s00262-021-03042-y

Keywords

Head and neck squamous cell carcinoma; Nivolumab; Treatment response; T lymphocyte

Funding

  1. Ministry of Education, Culture, Sports, Science and Technology [20K18243, 20K09747, 19K18794, 19K18758, 20H03834]
  2. Ministry of Agriculture, Forestry and Fisheries of Japan (Research Project for Sericultural Revolution), Japan
  3. Grants-in-Aid for Scientific Research [20H03834, 20K18243, 20K09747, 19K18758, 19K18794] Funding Source: KAKEN

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This study found that in patients with recurrent/metastatic HNSCC treated with nivolumab, circulating T cells show dynamic alterations in activation status and immune checkpoint molecule expression levels, which may be associated with treatment response. The frequency of MAGE-A4-specific T cells significantly increased in patients with disease control.
Cancer immunotherapy using immune checkpoint inhibitors (ICIs) has been recognized as a novel therapeutic option for head and neck squamous cell carcinoma (HNSCC). However, only approximately 20-30% of patients with recurrent/metastatic (R/M) HNSCC benefit. Moreover, the mechanisms underlying the response to ICIs remain unclear. We investigated the proportion, activation status, and expression level of immune checkpoint molecules in circulating T cell subsets in R/M HNSCC patients treated with nivolumab using flow cytometry and mass cytometry, and then determined whether treatment response was associated with these values. We also assessed the changes in the frequency of tumor-associated antigens, MAGE-A4 and p53, -specific T cells prior to and after nivolumab treatment using the IFN-gamma ELISPOT assay. The proportion of activated CD4+ and CD8+ TEMRA cells significantly increased in the disease-controlled patients but not in disease-progressed patients. As expected, the expression of PD-1 in T cells markedly decreased regardless of the therapeutic response. Meanwhile, T cell immunoglobulin mucin-3 expression on CD8+ T cells was significantly higher in patients with disease progression than in disease-controlled patients after treatment. The frequency of the tumor-associated antigens, MAGE-A4- and p53-specific T cells, was not correlated with clinical responses; however, in the disease-controlled patients, the frequency of MAGE-A4-specific T cells was significantly augmented. We concluded that in R/M HNSCC patients treated with nivolumab, circulating T cells show dynamic alterations depending on treatment efficacy. An analysis of the immunokinetics of circulating T cells could thus provide new insights into rational therapeutic strategies in cancer immunotherapy for HNSCC.

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