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Immunopathologic changes in patients with cutaneous malignant melanoma following intratumoral inoculation of BCG: Correlation with cell‐mediated immunity
Author(s) -
Lieberman Ronald,
Epstein William,
Fudenberg H. H.
Publication year - 1974
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.2910140315
Subject(s) - melanoma , medicine , immune system , antigen , peripheral blood mononuclear cell , immunology , immunotherapy , cellular immunity , immunity , cancer research , biology , in vitro , biochemistry
Six patients with cutaneous melanoma were treated with intratumoral Bacillus Calmette‐Guérin (BCG). Four showed good responses with regression of injected and, frequently, of uninjected lesions, whereas two developed dissemination and died. Three of four responders remain in complete remission. Two straìns of BCG were used; there was no detectable difference in therapeutic efficacy. Three of four responders showed a significant increase in lymphocyte stimulation (LS) to melanoma antigens, and all responders showed a marked increase in phytohemagglutinin (PHA). Non‐responders showed no increase to either stimulant. All responders were negative for leukocyte migration inhibition (LMI) to melanoma antigens before BCG, but two of four responders converted to positive after BCG therapy. Of the non‐responders, one was positive and one was negative before therapy; there was no change following BCG. There was a marked increase in active rosette‐forming cells (RFCS) in all responders and in only one of two non‐responders. Preliminary studies suggest that BCG also affects the level of circulating inhibitors which abrogate the activity of immune lymphocytes to melanoma antigens. A definite sequence occurs following intratumoral BCG: (1) disruption of melanogenesis with release of pigment from tumor cells (3‐6 h); (2) inflammatory response of polymorphonuclear leukocytes (PMNS) and mononuclear cells which remain at the tumor periphery (6‐24h); (3) tumor‐cell death (24h); and (4) granulomas replacing tumor (2 weeks). The response to BCG resembles the immunologic and histopathologic changes observed in halo nevi. These studies suggest that BCG activates both tumor‐specific and non‐specific immune responses. Thus, in vitro parameters of cell‐mediated immunity (CMI) are affected by BCG and some, particularly LS, LMI and the active rosette test, seem to correlate with clinical response.