Bystander activation in memory and antigen-inexperienced memory-like CD8 T cells

Paprčková, Darina; Salyova, Eva; Michálik, Juraj; Štěpánek, Ondřej

doi:10.1016/j.coi.2023.102299

Cited by 8 publications

(3 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…NL-201 has the capacity to activate antigen-specific CD8 T cells and antigen-nonspecific innate-like virtual memory CD8 T cells, consistent with previous literature using IL-15 mimetics. 50 , 51 , 52 The latter bystander-activated CD8 T cells have been described to mediate immunity in the absence of TCR engagement, typically via the NKG2D pathway. 50 , 51 , 52 Myeloma rechallenge experiments in our study confirmed that the protective immunity generated in the context of NL-201 was completely antigen-dependent.…”

Section: Discussionmentioning

confidence: 99%

“… 50 , 51 , 52 The latter bystander-activated CD8 T cells have been described to mediate immunity in the absence of TCR engagement, typically via the NKG2D pathway. 50 , 51 , 52 Myeloma rechallenge experiments in our study confirmed that the protective immunity generated in the context of NL-201 was completely antigen-dependent. Given this, myeloma-specific CD8 T cells rather than bystander CD8 innate-like virtual memory T cells are the predominant cell population mediating myeloma immunity after NL-201 treatment during stem cell mobilization.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Regulatory T cells suppress myeloma-specific immunity during autologous stem cell mobilization and transplantation

Takahashi,

Minnie,

Ensbey

et al. 2024

Blood

View full text Add to dashboard Cite

Autologous stem cell transplantation (ASCT) is the standard of care consolidation therapy for eligible patients with myeloma but most patients eventually progress, an event associated with features of immune escape. Novel approaches to enhance anti-myeloma immunity after ASCT represents a major unmet need. Here, we demonstrate that patient mobilized stem cell grafts include high numbers of both effector CD8 T cells and immunosuppressive regulatory T cells (Treg). We show that BM residing T cells are efficiently mobilized during stem cell mobilization (SCM) and hypothesized that mobilized and highly suppressive BM-derived Tregs might limit anti-myeloma immunity during SCM. We thus undertook ASCT in a preclinical myeloma model with or without stringent Treg depletion during SCM. Treg depletion generated SCM grafts containing polyfunctional CD8 T effector memory cells that dramatically enhanced myeloma control after ASCT. We thus explored clinically tractable translational approaches to mimic this scenario. Antibody based approaches resulted in only partial Treg depletion and were inadequate to recapitulate this effect. In contrast, a synthetic IL-2/IL-15 mimetic which stimulates the IL-2 receptor on CD8 T cells without binding to the high affinity IL-2Ra utilized by Treg, efficiently expanded polyfunctional CD8 T cells in mobilized grafts and protected recipients from myeloma progression after ASCT. We confirm that Treg depletion during stem cell mobilization can mitigate constraints on tumor immunity and result in profound myeloma control after ASCT. Direct and selective cytokine signaling of CD8 T cells can recapitulate this effect and represents a clinically testable strategy to improve responses after ASCT.-

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Regulatory T cells suppress myeloma-specific immunity during autologous stem cell mobilization and transplantation

Takahashi,

Minnie,

Ensbey

et al. 2024

Blood

View full text Add to dashboard Cite

show abstract

“…The better effector signature genes [ 8 ] appear to overlap with the profile of human and murine bystander activated CD8 + T cells stimulated by IL-15 (reviewed in [ 24 ]), a cytokine that binds to IL-2Rβγ and uses the identical signaling pathway to IL-2. IL-15-based biologicals represent another promising direction of experimental anticancer therapy (reviewed in [ 25 ]).…”

Section: Strong Il-2 Signals Are Required For the Formation Of Better...mentioning

confidence: 99%

IL-2-driven CD8+ T cell phenotypes: implications for immunotherapy

Niederlova,

Tsyklauri,

Kovar

et al. 2023

Trends in Immunology

Self Cite

View full text Add to dashboard Cite

Elevated memory T‐cell conversion in a preclinical mouse model of hemophilia A

Kalandadze,

Di Simone,

Mohammed

et al. 2024

Eur J Immunol

View full text Add to dashboard Cite

One of the major challenges in the choice of the best therapeutic approach for the treatment of patients affected by hemophilia A (HA) is the definition of criteria predicting the formation of factor VIII (FVIII) neutralizing antibodies, called inhibitors. Both genetic and environmental elements influencing the immune response toward FVIII have been identified but still not all the factors causing the pathological rejection of FVIII have been identified. Since there is a connection between coagulation and inflammation, here we assessed the role played by the FVIII deficiency in shaping the humoral and cellular response toward an antigen other than FVIII itself. To this aim, we challenged both HA and wild‐type (WT) mice with either FVIII or ovalbumin (OVA) and followed antigen‐specific antibody level, immune cell population frequency and phenotype up to 9 weeks after the last antigen booster. The activation threshold was evaluated in vitro by stimulating the murine T cells with a decreasing dose of α‐CD3. The humoral response to FVIII was similar between the two groups while both the in vivo and in vitro experiments highlighted an antigen‐independent sensitivity of HA compared with WT T cells causing an increase in memory T‐cell conversion and proliferation capability.

show abstract

Bystander activation in memory and antigen-inexperienced memory-like CD8 T cells

Cited by 8 publications

References 45 publications

Regulatory T cells suppress myeloma-specific immunity during autologous stem cell mobilization and transplantation

Regulatory T cells suppress myeloma-specific immunity during autologous stem cell mobilization and transplantation

IL-2-driven CD8+ T cell phenotypes: implications for immunotherapy

Elevated memory T‐cell conversion in a preclinical mouse model of hemophilia A

Contact Info

Product

Resources

About