Lymphocyte Subpopulations Infiltrating Squamous Carcinomas of the Head and Neck: Correlations with Extent of Tumor and Prognosis

Because little is known about the mechanisms involved in local tumor-host immune reactions in squamous carcinoma of the head and neck, a study was undertaken to better characterize the types of immune cells present at the local tumor site and determine their relationship to tumor extent, systemic cellular immune parameters, and clinical outcome. In 40 untreated patients, lymphocyte subsets (LS) at the tumor-host interface were quantitated immunohistologically from serial sections of frozen tumor specimens and correlated with concurrently measured peripheral LS levels and in vitro lymphocyte reactivity to phytohemagglutinin (PHA). The majority of infiltrating lymphocytes were T cells with rare B or Leu 7 cells. Proportions of T₄ and T₈ were similar in peritumor stroma; however, T₈ cells predominated tumor parenchyma. Stromal and parenchymal infiltration by LS were not related to peripheral blood LS levels, lymphocyte reactivity, or tumor site. However, parenchymal T₁₁ and T₄ cell infiltration was less in advanced primary tumors (T3, T4) than in early tumors (T1, T2) (P = 0.01, P = 0.067, respectively), as was peripheral lymphocyte reactivity to PHA (P = 0.013). Short-term disease-free interval and actuarial survival differed significantly—according to parenchymal T₁₁ and T₄ cell infiltration—and were not related to T₈, leu 7, and B-cell infiltration. The findings extend prior studies of lymphocytic infiltration in head and neck cancer and demonstrate the potential importance of differences in tumor stromal and parenchymal infiltration. Together with recent evidence that T₄ cells are critical for lymphokine production and for the proliferation of cytotoxic effector cells, the current results suggest that T₄ cells play a critical role in the local immune response in squamous carcinoma of the head and neck.