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Toxicities of Immunotherapy for the Practitioner
#MMPMID25918278
Weber JS
; Yang JC
; Atkins MB
; Disis ML
J Clin Oncol
2015[Jun]; 33
(18
): 2092-9
PMID25918278
show ga
The toxicities of immunotherapy for cancer are as diverse as the type of
treatments that have been devised. These range from cytokine therapies that
induce capillary leakage to vaccines associated with low levels of autoimmunity
to cell therapies that can induce damaging cross-reactivity with normal tissue to
checkpoint protein inhibitors that induce immune-related adverse events that are
autoinflammatory in nature. The thread that ties these toxicities together is
their mechanism-based immune nature and the T-cell-mediated adverse events seen.
The basis for the majority of these adverse events is a hyperactivated T-cell
response with reactivity directed against normal tissue, resulting in the
generation of high levels of CD4 T-helper cell cytokines or increased migration
of cytolytic CD8 T cells within normal tissues. The T-cell immune response is not
tissue specific and may reflect a diffuse expansion of the T-cell repertoire that
induces cross-reactivity with normal tissue, effectively breaking tolerance that
is active with cytokines, vaccines, and checkpoint protein inhibitors and passive
in the case of adoptive cell therapy. Cytokines seem to generate diffuse and
nonspecific T-cell reactivity, whereas checkpoint protein inhibition, vaccines,
and adoptive cell therapy seem to activate more specific T cells that interact
directly with normal tissues, potentially causing specific organ damage. In this
review, we summarize the toxicities that are unique to immunotherapies,
emphasizing the need to familiarize the oncology practitioner with the spectrum
of adverse events seen with newly approved and emerging modalities.
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