Peripheral γδ T‐cell deficit in nasopharyngeal carcinoma

Abstract

Previous studies identified CD56؉ and CD56 ؊ subsets of peripheral ␥␦ T cells from healthy donors. Both subsets responded to stimulation by a myeloma cell line, XG-7 and undergo vigorous ex vivo expansion in the presence of exogenous IL-2. They are cytotoxic for different tumor targets including nasopharyngeal carcinoma, but they differ from one another in that the CD56 ؊ subset has an additional growth requirement for IL-7 and exhibited greater cytotoxicity against nasopharyngeal carcinoma (NPC) targets. These immune cells were further shown to retard tumor growth in a nude mice NPC model. To assess if these immune cells might contribute to host defense against NPC, we compared ␥␦ T-cell status of NPC patients with healthy donors and survivors who had been in clinical remission of the cancer. It was found that peripheral ␥␦ T cells of patients were impaired in their response to the stimulatory effects of XG-7 and exhibited weak or essentially no cytotoxicity for the NPC targets. The deficits were present in early and advanced stages of the cancer but were restored among survivors after successful treatment of the cancer. These findings support a role for peripheral ␥␦ T cells in host defense against NPC. It was noted that these immune cells comprise less than 5% of peripheral blood monocytic cells and hence it was not surprising that this component of host defense was breached early in the development of the cancer. © 2002 Wiley-Liss, Inc. Key words: ␥␦ T cells; immune deficit; NPC; tumor immunityT-cell immunity is the principal component of host defense against chronic infection and tumors. The effector arms are mainly composed of 2 subpopulations of cytotoxic T lymphocytes (CTLs) bearing TCR-␣␤ or -␥␦ chains. The ␣␤ CTLs recognize processed antigenic peptides bound to the major histocompatibility complex (MHC) and hence their effector functions are restricted to targets that express identical or related MHC. The ␥␦ T cells effect non-MHC-restricted killing. Although ␥␦ T cells constitute only 1-10% of circulating T cells, recent studies have demonstrated that this minor subpopulation of T cells plays a more important role in the host immune defense than their relatively sparse numbers might suggest. 1,2 These 2 subpopulations of T cells are generally believed to serve a complementary role in host surveillance. However, the ultimate niche of ␥␦ T cells in human immune system is still unclear.A variety of human diseases have been demonstrated to associate with a selective proliferation of blood ␥␦ T cells. It was observed that ␥␦ T-cell numbers increased in patients with tuberculosis 1 (TB) and in healthy individuals in contact with TB patients. 3 In human ehrlichiosis, ␥␦ T cells represented a majority of blood lymphocytes that accounted for as much as 97% of circulating T cells at early stage for about 2 weeks before returning to a normal ␣␤/␥␦ ratio. 4 In the "silent" periods of celiac disease where pathology was mildest, it was found that the number of ␥␦ T cells was higher, suggesting that these cells may ...

Flow cytometric assessment of autologous γδ T cells in patients with acute myeloid leukemia: Potential effector cells for immunotherapy?

“…The frequency of gd T cells in our healthy control group was within the expected range (54,71). Our findings are in line with reports of a peripheral gd T cell deficit in patients with other types of malignancies such as cutaneous primary melanoma (68) and nasopharyngeal carcinoma (70). The possibility that low levels of circulating gd T cells may contribute to the failure of immune surveillance against AML is supported by studies of gd T lymphocyte-deficient mice: These animals are highly susceptible to cutaneous carcinogenesis (72) and colorectal adenocarcinoma can be readily induced (69).…”

“…We first examined gd T cell levels in AML patients at diagnosis since it has been suggested that the frequency of these cells plays a role in the balance between health and disease (3,67), and that an impairment of T cells expressing g/d TCRs may lead to a downregulation of normal immune defense (68)(69)(70). In this regard, it is of interest that in patients with advanced stage solid tumors a correlation between low gd T cell counts and short survival time has been reported (58).…”

Antitumor Activity of γδ T Cells Reactive against Cytomegalovirus-Infected Cells in a Mouse Xenograft Tumor Model

“…In agreement with their potential role in tumor host defense in vivo, gy T cells have been found with an increased frequency in peripheral blood mononuclear cells from disease-free survivors of leukemia after allogeneic bone marrow transplantation (14,15). It was also reported that the reactivity of peripheral gy T cells against nasopharyngeal carcinoma was impaired in cancer patients, whereas the deficit was restored among survivors after successful treatment (16).…”

What lessons can be learned from γδ T cell-based cancer immunotherapy trials?

“…[5][6][7] cd TILs, primarily of the Vc9Vd2 cd T cell type, were reported in renal cell carcinomas, albeit with controversial prognostic values. [7][8][9][10] Nasopharyngeal carcinoma patients carry Vc9Vd2 cd T lymphocytes that are functionally impaired in blood 11 but are able to infiltrate and reduce xenografted nasopharyngeal tumors in mice. 12 Likewise, orthotopic xenografts of breast tumors 13 or bladder carcinomas 14 in mice infused with human TCRVc9Vd2 1 lymphocytes also show strong tumor infiltration by cd TILs and subsequent arrest of tumor growth.…”