Adoptive CD8+ T cell therapy against cancer:Challenges and opportunities

Jiang, Xiaotao; Jiang, Xu; Liu, Mingfeng; Xing, Hui; Wang, Zhiming; Huang, Lei; Mellor, Andrew L.; Wang, Wei; Wu, Sha

doi:10.1016/j.canlet.2019.07.017

Cited by 102 publications

(67 citation statements)

References 95 publications

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“…From tumor infiltrating lymphocytes to T-cell receptor (TCR) and chimeric antigen receptor (CAR) T-cell engineering, T cells have marked important milestones in cancer immunotherapy [ 1 ]. T cells recognize short peptide epitopes in the context of the major histocompatibility complex (MHC) thanks to their TCR.…”

Section: Introduction To Tcr Affinity Avidity and Functional Avimentioning

confidence: 99%

The Quest for the Best: How TCR Affinity, Avidity, and Functional Avidity Affect TCR-Engineered T-Cell Antitumor Responses

Campillo-Davò

Flumens

Lion

2020

Cells

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Over the past decades, adoptive transfer of T cells has revolutionized cancer immunotherapy. In particular, T-cell receptor (TCR) engineering of T cells has marked important milestones in developing more precise and personalized cancer immunotherapies. However, to get the most benefit out of this approach, understanding the role that TCR affinity, avidity, and functional avidity play on how TCRs and T cells function in the context of tumor-associated antigen (TAA) recognition is vital to keep generating improved adoptive T-cell therapies. Aside from TCR-related parameters, other critical factors that govern T-cell activation are the effect of TCR co-receptors on TCR–peptide-major histocompatibility complex (pMHC) stabilization and TCR signaling, tumor epitope density, and TCR expression levels in TCR-engineered T cells. In this review, we describe the key aspects governing TCR specificity, T-cell activation, and how these concepts can be applied to cancer-specific TCR redirection of T cells.

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Section: Introduction To Tcr Affinity Avidity and Functional Avimentioning

confidence: 99%

The Quest for the Best: How TCR Affinity, Avidity, and Functional Avidity Affect TCR-Engineered T-Cell Antitumor Responses

Campillo-Davò

Flumens

Lion

2020

Cells

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“…The strategy of blocking inhibitory signaling pathways in T lymphocytes has remarkable influenced cancer therapy 14,15 . Blocking immune checkpoint protein inhibitors, such as PD‐L1 and PD‐1, have shown effectiveness against various solid tumors, including melanoma, non‐small‐cell lung cancer, and renal cancer 16,17 .…”

Section: Introductionmentioning

confidence: 99%

Bromo‐ and extraterminal domain protein inhibition improves immunotherapy efficacy in hepatocellular carcinoma

et al. 2020

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“…In tumor immunity, CD8 + T cells are the key cells against tumors [18]. They accumulate in tumor tissues, make physical contact with malignant tumor cells, and then kill tumors targetedly through activation signals from other cells [19].…”

Section: Introductionmentioning

confidence: 99%

Progranulin Induces Immune Escape in Breast Cancer Via Up-Regulating PD-L1 Expression on TAMS and Promoting CD8+T cell Exclusion

Fang

Zhou

Shi

et al. 2020

Preprint

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Background: Progranulin (PGRN), as a multifunctional growth factor, is overexpressed in multiple tumors, but the role of PGRN on tumor immunity is still unclear. Here, we studied the effect of PGRN on breast cancer tumor immunity and its possible molecular mechanism.Methods: The changes of macrophage phenotypes after PGRN treatment were detected by western blot, quantitative PCR and flow cytometry. Western blot was used to study the signal molecular mechanism of PGRN regulating this process. The number and localization of immune cells in WT and PGRN-/- breast cancer tissues were analyzed by immunohistochemical staining and immunofluorescence techniques. The activation and proliferation of CD8+ T cells were measured by flow cytometry.Results: After being treated with PGRN, the expressions of M2 markers and PD-L1 on macrophages increased. STAT3 signaling pathway inhibitor Stattic could significantly inhibit PD-L1 expression and M2 related markers induced by PGRN. In WT group, CD8 were co-localized with macrophages and PD-L1, but not tumor cells. The number of immune cells in PGRN-/- breast cancer tissue increased, and the infiltration into tumor parenchyma also increased. Moreover, in the co-culture system, WT peritoneal macrophages not only reduced the ratio of activated CD8+T cells but also reduced the proportion of proliferating CD8+T cells. The addition of PD-1 and PD-L1 neutralizing antibodies could effectively reverse this effect and restore the immune function of CD8+T cells.Conclusion: The results show that PGRN can promote M2 polarization and PD-L1 expression by activating the STAT3 signaling pathway. Furthermore, through PD-1/PD-L1 interaction, PGRN can promote the breast tumor immune escape. Our research may provide new ideas and targets for clinical breast cancer immunotherapy.

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Adoptive CD8+ T cell therapy against cancer:Challenges and opportunities

Cited by 102 publications

References 95 publications

The Quest for the Best: How TCR Affinity, Avidity, and Functional Avidity Affect TCR-Engineered T-Cell Antitumor Responses

The Quest for the Best: How TCR Affinity, Avidity, and Functional Avidity Affect TCR-Engineered T-Cell Antitumor Responses

Bromo‐ and extraterminal domain protein inhibition improves immunotherapy efficacy in hepatocellular carcinoma

Progranulin Induces Immune Escape in Breast Cancer Via Up-Regulating PD-L1 Expression on TAMS and Promoting CD8+T cell Exclusion

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