Requirement of innate immunity in tumor-bearing mice cured by adoptive immunotherapy using tumor-draining lymph nodes

Background: the purpose of this study was to determine the cellular effectors of both the adoptively transferred cells and the tumor-bearing host that participate in the antitumor response to adoptive immunotherapy using culture-activated tumor-draining lymph nodes (tdlns). methods: tdlns harvested frommice with 4t1 carcinoma cells were fractionated to derive the l-selectinlow subpopulation and activated ex vivo prior to in vitro cytokine release assays and adoptive transfer into balb/cmice bearing 3-day established subcutaneous tumors. tumor-bearing recipients were scid (lacking t,b,and nkcells),rag2 deficient (lacking t and b cells),and wild-type balb/c mice. results: culture-activated l-selectinlow 4t1 tdln from balb/c mice secreted significant levels of interferon-gamma in response to 4t1 but not control tumor cells in vitro. cd4 cells within the adoptively transferred effector cell population contributed significantly to the antitumor effect in vivo. culture-activated l-selectinlow tdlns from balb/c wild-type mice were able to cure rag2 deficient but not scid mice bearing 4t1 subcutaneous tumors,suggesting a requirement of nk cells within the innate immune system of the tumor-bearing host during the antitumor response. conclusions: these results identify the cellular effectors involved in tumor regression following adoptive transfer and demonstrate the requirement for intact innate immunity within the tumor-bearing host. copyright © 2015 john ammori et al.