Adoptive immunotherapy with IL-2 results in the loss of delayed-type hypersensitivity responses and the development of immediate hypersensitivity to recall antigens☆

Abstract Skin testing represents a direct method of assessing immune responses in vivo . Twenty-six patients with metastatic cancer of the lung, kidney, or melanoma were treated with adoptive transfers of autologous tumor-infiltrating or blood lymphocytes and continuous infusions of interleukin-2 (IL-2). Prior to therapy, cutaneous anergy to recall antigens was observed in 19 patients (73%), whereas 6 (27%) displayed normal delayed-type hypersensitivity (DTH) responses. When tested again at the end of therapy, DTH responses could not be elicited in any of the patients. Proliferative responses to skin test antigens, lectins, and IL-2 diminished progressively during therapy but returned to baseline values at 1 month. Unexpectedly, 14 of these patients (53%) developed immediate skin test responses to candida antigens and 5 (19%) to mumps antigens. These immediate responses were characterized by local erythema and induration that developed within minutes of injecting antigen. Biopsies displayed marked dermal edema and infiltration by eosinophils. Although serum IgE levels were not increased, immediate reactivity could be transferred by a heat-sensitive serum factor. The implications of this novel response are uncertain, and its development did not correlate directly with the anti-tumor effects of therapy. We conclude that adoptive immunotherapy with IL-2 produces a reduction in cutaneous DTH and diminished responses to mitogens while simultaneously promoting cutaneous allergy. We hypothesize that this may reflect diminished IL-2 production by antigen-specific helper T cells and that other lymphokines may promote these immediate hypersensitivity responses.