Abstract
Host conditioning has emerged as an important component of effective adoptive cell transfer-based immunotherapy for cancer. High levels of IL-1β are induced by host conditioning, but its impact on the antitumor function of T cells remains unclear. We found that the administration of IL-1β increased the population size and functionality of adoptively transferred T cells within the tumor. Most importantly, IL-1β enhanced the ability of tumor-specific T cells to trigger the regression of large, established B16 melanoma tumors in mice. Mechanistically, we showed that the increase in T cell numbers was associated with superior tissue homing and survival abilities and was largely mediated by IL-1β-stimulated host cells. In addition, IL-1β enhanced T cell functionality indirectly via its actions on radio-resistant host cells in an IL-2- and IL-15-dependent manner. Our findings not only underscore the potential of provoking inflammation to enhance antitumor immunity but also uncover novel host regulations of T cell responses.
Highlights
Adoptive transfer of antitumor T cells has shown great potential LPS in mice that received total body irradiation
Administration of IL-1β enhances the antitumor function of adoptively transferred CD8+ T cells We have previously demonstrated that the systemic administration of IL-1β increased cell numbers and granzyme B (Gzm B) expression of adoptively transferred OT-I CD8+ T cells in both lymphoid and nonlymphoid tissues in response to OVA/LPS immunization (Ben-Sasson et al, 2013a)
We demonstrate here that the administration of IL-1β can potentiate the efficacy of adoptively transferred antitumor T cells to mediate tumor regression
Summary
Adoptive transfer of antitumor T cells has shown great potential LPS in mice that received total body irradiation Given that IL-1β administration can enhance the autologous T cells genetically modified to express tumor- protective value of vaccines (Ben-Sasson et al, 2013a,b; Wüthrich reactive TCRs or chimeric antigen receptors can mediate dura- et al, 2013), we investigated its therapeutic potential in imble tumor regression in several malignancies Adoptive cell therapy (ACT)–based proved the efficacy of adoptively transferred T cells in mediating immunotherapy has made great strides forward in recent years, tumor regression by increasing their cell numbers and funcit remains ineffective for a majority of patients with common tionality within the tumor. Host lymphodepletion induced by relied on IL-1β–stimulated radio-resistant host cells in a TCR-
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