Identifying tumor antigen-specific T cells from cancer patients has important implications for immunotherapy diagnostics and therapeutics. Here, we show that CD103+CD39+ tumor-infiltrating CD8 T cells (CD8 TIL) are enriched for tumor-reactive cells both in primary and metastatic tumors. This CD8 TIL subset is found across six different malignancies and displays an exhausted tissue-resident memory phenotype. CD103+CD39+ CD8 TILs have a distinct T-cell receptor (TCR) repertoire, with T-cell clones expanded in the tumor but present at low frequencies in the periphery. CD103+CD39+ CD8 TILs also efficiently kill autologous tumor cells in a MHC-class I-dependent manner. Finally, higher frequencies of CD103+CD39+ CD8 TILs in patients with head and neck cancer are associated with better overall survival. Our data thus describe an approach for detecting tumor-reactive CD8 TILs that will help define mechanisms of existing immunotherapy treatments, and may lead to future adoptive T-cell cancer therapies.

We used end-point-dilution cultures to measure the level of infectious human immunodeficiency virus type 1 (HIV-1) in peripheral-blood mononuclear cells (PBMC) and plasma of 54 infected patients who were not receiving antiviral chemotherapy. HIV-1 was recovered from the plasma and PBMC of every seropositive patient, but from none of 22 seronegative control subjects. The mean titers in plasma were 30, 3500, and 3200 tissue-culture-infective doses (TCID) per milliliter for patients with asymptomatic infection, the acquired immunodeficiency syndrome (AIDS), and the AIDS-related complex, respectively. In PBMC, the mean titers were significantly higher for symptomatic patients (AIDS, 2200, and AIDS-related complex, 2700 TCID per 10(6) PBMC) than asymptomatic patients (20 TCID per 10(6) PBMC). The values for the symptomatic patients were considered to indicate that at least 1 in 400 circulating mononuclear cells harbored HIV-1. The HIV-1 titers of seven patients with AIDS or AIDS-related complex treated with zidovudine for four weeks decreased significantly in plasma but not in PBMC. In addition, the mean titer in the plasma of 20 patients receiving long-term zidovudine treatment (130 TCID per milliliter) was 25-fold lower than the mean for comparable untreated patients with AIDS or AIDS-related complex. We conclude that the levels of HIV-1 in plasma and PBMC are much higher than previous estimates. This high degree of HIV-1 viremia raises the possibility that the direct cytopathic effect of this retrovirus alone may be sufficient to explain much of the pathogenesis of AIDS.

Although p24 core antigenemia and viral isolation have previously been described during primary HIV-1 infection, this report documents the large viral burden during the acute phase of infection. The rapid and spontaneous decline in the viral load suggests an effective immune response in the host that, if understood, may be used to combat AIDS.