Sequential evaluation of cutaneous delayed hypersensitivity responses to recall and to lymphoid cell line antigens in Burkitt's lymphoma

Abstract

Delayed cutaneous hypersensitivity reactions to standard recall antigens (candidin, mumps and PPD), to crude membrane extracts of a cell line derived from Burkitt's lymphoma (Raji) and to cell line derived from normal lymphocytes (F265) were sequentially evaluated in 44 patients with Burkitt's lymphoma. Sixteen patients (36%) manifested delayed hypersensitivity responses to the standard antigens and seven (16%) to the Raji membrane extract at presentation. Following successful chemotherapy, there was prompt and significant improvement of reactivity to both the standard and Raji antigens (p greater than 0.001), suggesting that the initial impairment of delayed hypersensitivity was most likely related to tumor burden. By 9 months after treatment, all patients in sustained remission expressed reactivity to Raji and 21 of 22 to the standard antigens. None of the patients skin-tested with the F265 extract at presentation gave a positive response and only one subsequently expressed reactivity after remission was induced. On relapse, reactivity to the standard antigens was more readily lost (4 of 11) then reactivity to the Raji extract (1 of 7). Pretreatment delayed hypersensitivity to the standard antigens also correlated better with long-term survival than to pretreatment responses to Raji. It remains to be determined whether the antigens expressed in the Raji extract are indeed tumor-specific or related to Epstein-Barr virus.

Delayed hypersensitivity reactions of cancer patients to antigens on lymphoid cell lines

“…Stage of disease and treatment status, factors that have been shown to be important in our own studies (Fass et al, 1970;Nkrumah et al, 1977;Ho et al, in press) as well as those of others (Eilber and Morton, 1970) have been reviewed elsewhere but, while they were important considerations, they did not affect the disease pattern reported here. The closest link between antigen source and patient disease appears to be with HKLY-28 and NPC, an apparently augmented reactivity to this cell line being unrelated to the patients' ethnic origin or place of residence ( Table I, Levine et al, 1976).…”

“…Second, the skin test appears to be one of the best immunologic correlates of prognosis. Having been proven to be of extreme clinical importance in certain diseases such as tuberculosis and leprosy, skin testing has been noted to be of prognostic value in patients with melanoma, sarcoma, Burkitt's lymphoma (BL) and a number of other neoplasms (Eilber and Morton, 1970;Fass et al, 1970;Herberman, 1974;Nkrumah et al, 1977). Finally, as a test that is readily standardized and available to countries which do not have sophisticated laboratory technology available for clinical studies, the skin test has allowed us to initiate international collaborative studies in a number of countries interested in EBV immunity.…”

Sera from patients with undifferentiated nasopharyngeal carcinoma contain a factor which abrogates specific epstein‐barr virus antigen‐induced lymphocyte response

“…The in vivo significance of LSI remains to be defined; it is however important to note that, as in the case of many viral infections, a depression of cellmediated immunity can also be found in IM, BL and NPC patients (Fass et af., 1970;Bluming et af., 1971;Nkrumah et al, 1972;Notkins et al, 1973;Lai el al., 1974;Magrath, 1974;Woodruff and Woodruff, 1975;Ho et al, 1978;Wainwright et al 1979). Since the mechanism of such impaired cell-mediated immunity is not understood at present, the possibility that factors such as SBF and LSI are the principal (or sole?)…”

“…In contradistinction to anti-EA and anti-VCA titers mentioned above, high anti-body-dependent cellular cytotoxicity (ADCC) titers (Pearson et al, 1978) appear to be indicators of a good prognosis, while low titers point to a poor prognosis. Immunologically, a decrease in cell-mediated immunity has been found in NPC as well as in other EBVrelated diseases such as IM and BL (Fass, Herberman and Ziegler, 1970;Bluming et al, 1971;Nkrumah et al, 1972;Lai et al, 1974;Magrath, 1974;Ho et al, 1978;Wainwright et al, 1979). The mechanism of such impaired cell-mediated immunity is not yet understood.…”