Hepatocellular carcinoma (HCC) is the most common primary neoplasm of the liver and is one of the leading causes of cancer-related death worldwide. Liver transplantation (LT) has become one of the best curative therapeutic options for patients with HCC, although tumor recurrence after LT is a major and unaddressed cause of mortality. Furthermore, the factors that are associated with recurrence are not fully understood, and most previous studies have focused on the biological properties of HCC, such as the number and size of the HCC nodules, the degree of differentiation, the presence of hepatic vascular invasion, elevated serum levels of alpha-fetoprotein, and the tumor stage outside of the Milan criteria. Thus, little attention has been given to factors that are not directly related to HCC (i.e., "non-oncological factors"), which have emerged as predictors of tumor recurrence. This review was performed to assess the effects of non-oncological factors on tumor recurrence after LT. The identification of these factors may provide new research directions and clinical strategies for the prophylaxis and surveillance of tumor recurrence after LT, which can help reduce recurrence and improve patient survival.

The authors examined peripheral blood mononuclear cells from 45 patients with bronchogenic carcinoma to determine natural killer (NK) and lymphokine-activated killer (LAK) activity after in vitro incubation with media alone or media plus interferon gamma (IFN, 200 U/ml) and/or interleukin-2 (IL-2, 100 U/ml). Our results show that lymphocytes from patients with bronchogenic carcinoma can acquire LAK activity, but the level of activity acquired was significantly lower compared with lymphocytes from 25 control subjects when IL-2 cultures were supplemented with 10% autologous human serum (AHS) (15.6% +/- 2.1% specific release versus 26.0% +/- 2.9% specific release, P = 0.004). The LAK activity, defined as cytotoxicity of an NK-resistant cell line, of the patients' lymphocytes was augmented when cells were cultured with both IL-2 and IFN compared with IL-2 alone (P = 0.0001, paired t-test). Control subjects were unchanged (P = 0.09). There was no significant difference between groups of patients with different histologic types of tumor or different stages of disease. The NK activity, defined as killing of NK-sensitive K-562 target cells, of the patients' lymphocytes was not significantly different from that of the controls' lymphocytes (42.8% +/- 3.0% specific release versus 49.3% +/- 3.3% specific release, P = 0.16). These studies indicate the feasibility of IL-2 and IFN therapy in patients with bronchogenic carcinoma.

Although clusters of individuals infected with the human T-cell lymphotrophic virus type I (HTLV-I) have been identified in the United States, no systematic evaluation of the immunologic status of these persons has been reported. We therefore studied a group of 11 HTLV-I-infected former intravenous drug abusers who were long-term participants in a methadone maintenance program in New Orleans, Louisiana, to determine the effects of HTLV-I and chronic opiate use on immunity.

Mitogenic responses and results of serologic studies, cell phenotype analysis, and cytotoxicity assays were compared to those in two other HTLV-I seronegative groups: a similar group of 17 methadone users and 15 healthy age-, sex-, and race-matched control subjects. All study participants were seronegative for human immunodeficiency virus type 1.

Percentages and numbers of total T lymphocytes (CD2+,CD3+), T-suppressor/cytotoxic lymphocytes (CD8+), cytotoxic lymphocytes (Leu7+, Leu11+, NKH-1+) and B lymphocytes (B4+) were similar among the study groups. Although percentages and numbers of total T-helper lymphocytes (CD4+) were also similar among the groups, HTLV-I-infected subjects had higher percentages and proportions of helper/inducer cells (CD4:4B4+) than did HTLV-I seronegative methadone users. Both methadone using groups had decreased percentages and numbers of suppressor/inducer T lymphocytes (CD4:2H4+). Major histocompatibility complex unrestricted T-cell cytotoxicity (lectin-dependent cellular cytotoxicity), natural killer cell function, and mitogenic responses to the T-cell mitogen phytohemagglutin were similar among the three study groups. Pokeweed mitogen responses were severely depressed in the HTLV-I-infected population.

We conclude that HTLV-I infection is associated with abnormalities in T-cell-dependent B-cell proliferative responses. Furthermore, both long-term methadone use and HTLV-I infection are associated with abnormalities in the distribution of CD4+ cell subpopulations. The increase in the helper/inducer and T-cell cell populations and decrease in the pokeweed mitogenic response noted in HTLV-I-infected subjects appear to be markers for infection with this retrovirus.

Biologic response modifiers (BRM) such as interleukin-2 (Il-2) and gamma-interferon (gamma IFN) can augment preexisting or initiate new cytotoxic capacity of human lymphocytes against tumor cells. Although in vivo therapy with BRM or adoptive immunotherapy with BRM-treated cells seems logical in the treatment of bronchogenic carcinoma, recent studies have shown that lymphocytes from the lung and tumor tissues of patients with bronchogenic carcinoma have defective cytotoxic function. We sought to determine if defects in lung cytotoxic cell function are primary or secondary to local tumor effects, and if peripheral blood lymphocyte populations from patients can serve as a source for BRM-stimulated cytotoxic cells. We evaluated the natural killer (NK) cell and lymphokine (Il-2) activated killer cell activity (LAK) activity of mononuclear cell populations from 11 patients with newly diagnosed bronchogenic carcinoma and three control groups. Cultured human squamous cell and adenocarcinoma cell lines proved useful in evaluating LAK activity in these studies. Levels of NK and LAK activity in patients compared favorably with both those of non-smokers in two different age ranges and with smokers. Peripheral blood cytotoxic cell function remains intact and responsive to augmentation by BRM in patients with recently diagnosed bronchogenic carcinoma. Reported defects in patient lung cell cytotoxic function appear to be local tumor-related defects not present in peripheral blood lymphocytes.