Adoptively transferred effector cells derived from naïve rather than central memory CD8 ⁺ T cells mediate superior antitumor immunity

Abstract

Effector cells derived from central memory CD8 ؉ T cells were reported to engraft and survive better than those derived from effector memory populations, suggesting that they are superior for use in adoptive immunotherapy studies. However, previous studies did not evaluate the relative efficacy of effector cells derived from naïve T cells. We sought to investigate the efficacy of tumor-specific effector cells derived from naïve or central memory T-cell subsets using transgenic or retrovirally transduced T cells engineered to express a tumor-specific T-cell receptor. We found that naïve, rather than central memory T cells, gave rise to an effector population that mediated superior antitumor immunity upon adoptive transfer. Effector cells developed from naïve T cells lost the expression of CD62L more rapidly than those derived from central memory T cells, but did not acquire the expression of KLRG-1, a marker for terminal differentiation and replicative senescence. Consistent with this KLRG-1 ؊ phenotype, naïve-derived cells were capable of a greater proliferative burst and had enhanced cytokine production after adoptive transfer. These results indicate that insertion of genes that confer antitumor specificity into naïve rather than central memory CD8 ؉ T cells may allow superior efficacy upon adoptive transfer.

Complementary costimulation of human T-cell subpopulations by cluster of differentiation 28 (CD28) and CD81

“…Interestingly, the adoptive transfer of naïve T cells was shown to mediate a superior antitumor immunity (36). Our study provides insight regarding the preferential activation of naive T cells and may be useful in manipulating diseases of the immune system, such as autoimmunity and cancer.…”

Multivalent immunity targeting tumor-associated antigens by intra-lymph node DNA-prime, peptide-boost vaccination

“…In addition, it has been suggested that the effector profile and other less well-understood properties of discrete TAA-specific T-cell subpopulations may also have an important role in tumor regression. 24 Thus, in light of our data and additional information generated independently, 25,26 we re-evaluated the strengths and limitations of plasmid-based immunization as an option for active immunotherapy in cancer. More specifically, we sought to integrate the concept of immunization by direct intra-lymph node administration with a plasmid prime/peptide boost approach in an attempt to synergize key features of these two immunizing vectors: (i) plasmid priming for induction of a highquality immune response and (ii) peptide boosting for amplification and functional conversion of the immune response.…”

Polyfunctional response by ImmTAC (IMCgp100) redirected CD8+ and CD4+ T cells

“…In both mouse and non‐human primate studies, adoptively transferred CD8 + Tem cells rapidly developed into effector cells and efficiently killed tumour cells but only Tcm cells formed a persistent reservoir of functional T cells, occupied memory cell niches and provided a lasting anti‐cancer immune response 12, 13. Comparisons have also been made between the Tcm and naive CD8 + T cell repertoires and, although the findings are somewhat conflicting, both subpopulations bring a specific contribution to successful tumour elimination 14, 15, 16. Despite their crucial role in tumour clearance, CD8 + T cells on their own are not capable of delivering a sustained cancer remission.…”