Tumour-infiltrating lymphocytes mediate lysis of autologous squamous cell carcinomas of the head and neck

Abstract

Tumour-infiltrating lymphocytes (TIL) and tumours from six patients with squamous cell carcinomas of the head and neck (SCCHN) were investigated. The six tumours all expressed major histocompatibility complex (MHC) class I antigens both in vivo and as tumor cell lines grown in vitro. In addition, the cancer cells either overexpressed the tumour-suppressor gene product p53 or harboured human papilloma virus 16/18 (HPV). The TIL were expanded in vitro in the presence of interleukin-2, immobilised anti-CD3 mAb and soluble anti-CD28 mAb. Expanded TIL cultures contained both CD4+ and CD8+ T cells, but generally contained few CD56+CD3- cells of the natural killer (NK) phenotype. CD8+ T cells dominated the individual TIL cultures from five of the six patients and showed significant autologous tumour cell lysis. In TIL cultures derived from four of these tumour-reactive TIL cultures, killing could be partially blocked by an anti-MHC class I mAb. TIL cultures reacting with autologous tumour cells also showed strong TCR/CD3-redirected cytotoxicity when assayed against hybridoma cells expressing anti-TCR/CD3 mAb as well as natural-killer(NK)-like activity. A number of TIL cultures devoid of autologous tumour cell lysis were capable of lysing the natural-killer(NK)-sensitive K562 cell line suggesting that the SCCHN cells themselves are resistant to NK-like lysis. In conclusion, TIL cultures from head and neck carcinomas contain T cells which, upon expansion in vitro, can lyse autologous tumour cells in a MHC-class-I-restricted fashion. Thus, the results of the present study document that carcinomas of the head and neck in some patients are infiltrated by cytotoxic T cell precursors potentially capable of rejecting the autologous tumour.

An immunohistochemical study of altered immunomodulatory molecule expression in head and neck squamous cell carcinoma

“…Cytotoxic T-lymphocytes have also been isolated in vitro from tumour-infiltrating lymphocytes within HNSCC biopsies, and they demonstrate MHC class I restricted killing of HPV-infected SCC cells (Hald et al, 1995). Whether the loss of the HLA-B7 allele in HNSCC has prognostic implications similar to that in cervical cancer has still to be determined.…”

Spontaneous human squamous cell carcinomas are killed by a human cytotoxic T lymphocyte clone recognizing a wild-type p53-derived peptide

“…Conditions for removing, phenotyping, and culturing squamous carcinoma cells from head and neck cancer patients have been described (20). In brief, small pieces of carcinoma tissue were plated in culture medium.…”

“…Immunocytological evaluation was performed as described (20). In short, SCCHN cells were grown on chamber slides (Nunc), fixed in 10% formaldehyde for 2 h, and incubated with mAb against p53 (D0-7; Dako).…”

“…We quantitated the T cells infiltrating squamous cell carcinomas of head and neck (SCCHN) cancer patients (19,20). T-cell infiltration was found to be strongly correlated with the capability to propagate tumor infiltrating T lymphocytes in vitro.…”

“…T-cell infiltration was found to be strongly correlated with the capability to propagate tumor infiltrating T lymphocytes in vitro. Some of these propagated tumor infiltrating T lymphocyte cultures displayed a CD3 ϩ CD8 ϩ phenotype and were capable of killing autologous tumor cells in an MHC-Irestricted fashion (20). Immunohistological examinations showed that 23 of 44 SCCHN overexpressed the p53 protein (19).…”