CD5 expression by dendritic cells directs T cell immunity and sustains immunotherapy responses

He, Mingyu; Roussak, Kate; Ma, Feiyang; Borcherding, Nicholas; Garin, Vince; White, J. Michael; Schutt, Charles R.; Jensen, Trine I.; Zhao, Yun; Iberg, Courtney A.; Shah, Kairav; Bhatia, Himanshi; Korenfeld, Daniel; Dinkel, Sabrina; Gray, Judah; Antonova, Alina Ulezko; Ferris, Stephen T.; Donermeyer, David L.; Arlehamn, Cecilia S. Lindestam; Gubin, Matthew M.; Luo, Jingqin; Gorvel, Laurent; Pellegrini, Matteo; Sette, Alessandro; Tung, Thomas; Bak, Rasmus O.; Modlin, Robert L.; Fields, Ryan C.; Schreiber, Robert D.; Allen, Paul M.; Klechevsky, Eynav

doi:10.1126/science.abg2752

Cited by 41 publications

(25 citation statements)

References 100 publications

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“…An outstanding question in any study of T cell self-affinity is the effect of the CD5 molecule itself on the phenomena under investigation. With the important caveat of a very intriguing recent study into the importance of CD5 in T cell-DC interactions (He et al, 2023), the molecule proves surprisingly resilient to close inspection--likely due to the difficulty in teasing apart its effects in the thymus during development and in peripheral functioning. Thus, when stratifying T cells along CD5 and observing subsequent functional differences between the cells, it is tempting to ascribe those differences to the as-yet full undefined functioning of the molecule itself.…”

Section: Discussionmentioning

confidence: 99%

Thymically imprinted differential responsivity of naïve CD4 T cells to IL2 results in a heterogeneity of both Treg induction and subsequent effector functioning

Pennock,

Qian,

Ishihara

et al. 2023

Preprint

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Thymic selection predisposes naive T cells to particular outcomes when challenged later with cognate antigen, whether the antigen is self or foreign. This suggests that there is an inherent heterogeneity of functioning among T cells within the naive population (both CD4 and CD8s), and that each T cell, as part of its thymic development, is given a certain ‘programming’ which will affect its eventual fate decisions. In this project, we looked at the primary effects of this thymic imprinting on the conversion of naïve CD4 T cells into Tregs. Further, using an induced-Treg-reporter system, we exam the impact of thymic imprinted heterogeneity on effector functionality and identity stability. We report that naïve T cell differential responsivity to cytokines leads to the observed difference in Treg induction, and that the Tregs induced from T cells of different self-affinities maintain a heterogeneity of effector function and identity.

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Section: Discussionmentioning

confidence: 99%

Thymically imprinted differential responsivity of naïve CD4 T cells to IL2 results in a heterogeneity of both Treg induction and subsequent effector functioning

Pennock,

Qian,

Ishihara

et al. 2023

Preprint

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“…Crosstalk between cDC could be possible through IL-12 production—needed for the efficient induction of Th1 responses by cDC2s—or via CD40L-expressing CD4 T-cells [ 34 ]. Notably, a recent study by the group of E. Klechevsky revealed the crucial role of CD5 + CD1c + cDC2s in driving anti-tumor immunity and sustaining immunotherapy responses [ 49 ].…”

Section: DC Subsets In Melanoma: Heterogeneity Function Subversion An...mentioning

confidence: 99%

Dendritic Cell Subsets in Melanoma: Pathophysiology, Clinical Prognosis and Therapeutic Exploitation

Cuevas

Saas

Aspord

2023

Cancers

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Evasion from immunity is a hallmark of cancer development. Dendritic cells (DCs) are strategic immune cells shaping anti-tumor immune responses, but tumor cells exploit DC versatility to subvert their functions. Unveiling the puzzling role of DCs in the control of tumor development and mechanisms of tumor-induced DC hijacking is critical to optimize current therapies and to design future efficient immunotherapies for melanoma. Dendritic cells, crucially positioned at the center of anti-tumor immunity, represent attractive targets to develop new therapeutic approaches. Harnessing the potencies of each DC subset to trigger appropriate immune responses while avoiding their subversion is a challenging yet promising step to achieve tumor immune control. This review focuses on advances regarding the diversity of DC subsets, their pathophysiology and impact on clinical outcome in melanoma patients. We provide insights into the regulation mechanisms of DCs by the tumor, and overview DC-based therapeutic developments for melanoma. Further insights into DCs’ diversity, features, networking, regulation and shaping by the tumor microenvironment will allow designing novel effective cancer therapies. The DCs deserve to be positioned in the current melanoma immunotherapeutic landscape. Recent discoveries strongly motivate exploitation of the exceptional potential of DCs to drive robust anti-tumor immunity, offering promising tracks for clinical successes.

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“…pseudoprogression), and delayed time to treatment response. 5,29 As a family member of conventional imaging response criteria, Refined Response Evaluation Criteria in Solid Tumurs version 1.1.…”

Section: Imaging Response Criteria Of Lung Cancer Immunotherapymentioning

confidence: 99%

“…Several key differences in the response patterns of ICIs therapeutic agents compared with traditional tumour treatments include the potential initial transient worsening of disease burden, either through lesion enlargement or the appearance of new lesions (i.e. pseudoprogression), and delayed time to treatment response 5,29 …”

Section: Introductionmentioning

confidence: 99%

Radiological assessment of immunotherapy effects and immune checkpoint‐related pneumonitis for lung cancer

Wang

et al. 2023

J Cellular Molecular Medi

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Immune checkpoint inhibitors (ICIs) therapy have revolutionized advanced lung cancer care. Interestingly, the host responses for patients received ICIs therapy are distinguishing from those with cytotoxic drugs, showing potential initial transient worsening of disease burden, pseudoprogression and delayed time to treatment response. Thus, a new imaging criterion to evaluate the response for immunotherapy should be developed. ICIs treatment is associated with unique adverse events, including potential life‐threatening immune checkpoint inhibitor‐related pneumonitis (ICI‐pneumonitis) if treated patients are not managed promptly. Currently, the diagnosis and clinical management of ICI‐pneumonitis remain challenging. As the clinical manifestation is often nonspecific, computed tomography (CT) scan and X‐ray films play important roles in diagnosis and triage. This article reviews the complications of immunotherapy in lung cancer and illustrates various radiologic patterns of ICI‐pneumonitis. Additionally, it is tried to differentiate ICI‐pneumonitis from other pulmonary pathologies common to lung cancer such as radiation pneumonitis, bacterial pneumonia and coronavirus disease of 2019 (COVID‐19) infection in recent months. Maybe it is challenging to distinguish radiologically but clinical presentation may help.

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CD5 expression by dendritic cells directs T cell immunity and sustains immunotherapy responses

Cited by 41 publications

References 100 publications

Thymically imprinted differential responsivity of naïve CD4 T cells to IL2 results in a heterogeneity of both Treg induction and subsequent effector functioning

Thymically imprinted differential responsivity of naïve CD4 T cells to IL2 results in a heterogeneity of both Treg induction and subsequent effector functioning

Dendritic Cell Subsets in Melanoma: Pathophysiology, Clinical Prognosis and Therapeutic Exploitation

Radiological assessment of immunotherapy effects and immune checkpoint‐related pneumonitis for lung cancer

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