Functional virus-specific memory T cells survey glioblastoma

Ning, Jianfang; Gavil, Noah Veis; Wu, Shaoping; Wijeyesinghe, Sathi; Weyu, Eyob; Ma, Jun; Li, Ming; Grigore, Florina; Dhawan, Sanjay; Skorput, Alexander G. J.; Musial, Shawn C; Chen, Clark C.; Masopust, David; Rosato, Pamela C.

doi:10.1007/s00262-021-03125-w

Cited by 21 publications

(17 citation statements)

References 46 publications

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“…As seen previously, EBV-specific T cells in the tumor expressed CD69 and CD103 (Fig. 5g) 29,39 . We found that over 70% of both CD69+CD103+ EBV-specific T RM and non-viral specific T RM expressed CD39 to similar levels ( Fig.…”

Section: Resultssupporting

confidence: 79%

CD39 is expressed on functional effector and tissue resident memory CD8+ T cells

Isaacs,

Degefu,

Chen

et al. 2024

Preprint

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The ecto-ATPase CD39 is expressed on exhausted CD8+ T cells in chronic viral infection and has been proposed as a marker of tumor-specific CD8+ T cells in cancer, but the role of CD39 in an effector and memory T cell response has not been clearly defined. We report that CD39 is expressed on antigen-specific CD8+ short-lived effector cells (SLECs), while its co-ecto-enzyme, CD73, is found on memory precursor effector cells (MPEC) in vivo. Inhibition of CD39 enzymatic activity during in vitro T cell priming enhances MPEC differentiation in vivo after transfer and infection. The enriched MPEC phenotype is associated with enhanced tissue resident memory (TRM) establishment in the brain and salivary gland following an acute intranasal viral infection, suggesting that CD39 ATPase activity plays a role in memory CD8+ T cell differentiation. We also show that CD39 is expressed on human and murine TRM across several non-lymphoid tissues and melanoma, while CD73 is expressed on both circulating and resident memory subsets in mice. In contrast to exhausted CD39+ T cells in chronic infection, CD39+ TRM are fully functional when stimulated ex vivo with cognate antigen. This work further expands the identity of CD39 beyond a T cell exhaustion marker.

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Section: Resultssupporting

confidence: 79%

CD39 is expressed on functional effector and tissue resident memory CD8+ T cells

Isaacs,

Degefu,

Chen

et al. 2024

Preprint

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“…Viral peptide‐treated ex vivo human tumors recapitulated immune activation gene profiles observed in mice. Similarly, virus specific CD8+ T cells also populate mouse and human glioblastomas, which are one of the most aggressive and treatment‐resistant cancers 196 . Thus, these studies suggest that intratumoral delivery of viral peptide triggers local immune activation and activating viral bystander cells in TILs represents an alternative or complementary approach to tumor antigen‐specific TIL activation in cancer immunotherapy.…”

Section: Cancer Antigen‐specific T Cellsmentioning

confidence: 88%

Antigen‐specific and cross‐reactive T cells in protection and disease

Jiang

Malone

Chizari

2023

Immunological Reviews

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Human T cells have a diverse T-cell receptor (TCR) repertoire that endows them with the ability to identify and defend against a broad spectrum of antigens. The universe of possible antigens that T cells may encounter, however, is even larger. To effectively surveil such a vast universe, the T-cell repertoire must adopt a high degree of crossreactivity. Likewise, antigen-specific and cross-reactive T-cell responses play pivotal roles in both protective and pathological immune responses in numerous diseases. In this review, we explore the implications of these antigen-driven T-cell responses, with a particular focus on CD8+ T cells, using infection, neurodegeneration, and cancer as examples. We also summarize recent technological advances that facilitate highthroughput profiling of antigen-specific and cross-reactive T-cell responses experimentally, as well as computational biology approaches that predict these interactions.

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“…Wakim et al 13,40 found that virus-specific T RM cells in the brain die rapidly upon isolation from the resident tissue and fail to undergo recall expansion after adoptive transfer into the bloodstream of an antigen-challenged recipient, indicating that these cells depend on the local milieu for their function and survival. Ning and colleagues 41 found that injection of a viral antigen peptide converted infused memory T cells to a T RM phenotype in brain tumors but did not induce rejection of the tumors. Here, we were able to transfer CD8 + T RM cells into the brains of both immunocompetent and T cell-deficient naïve mice and induce a tumor-specific reaction in the recipient mice.…”

Section: Discussionmentioning

confidence: 99%

FGL2-targeting T cells exhibit antitumor effects on glioblastoma and recruit tumor-specific brain-resident memory T cells

Zhao

Kong

et al. 2023

Nat Commun

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Although tissue-resident memory T (TRM) cells specific for previously encountered pathogens have been characterized, the induction and recruitment of brain TRM cells following immune therapy has not been observed in the context of glioblastoma. Here, we show that T cells expressing fibrinogen-like 2 (FGL2)–specific single-chain variable fragments (T-αFGL2) can induce tumor-specific CD8+ TRM cells that prevent glioblastoma recurrence. These CD8+ TRM cells display a highly expanded T cell receptor repertoire distinct from that found in peripheral tissue. When adoptively transferred to the brains of either immunocompetent or T cell-deficient naïve mice, these CD8+ TRM cells reject glioma cells. Mechanistically, T-αFGL2 cell treatment increased the number of CD69+CD8+ brain-resident memory T cells in tumor-bearing mice via a CXCL9/10 and CXCR3 chemokine axis. These findings suggest that tumor-specific brain-resident CD8+ TRM cells may have promising implications for the prevention of brain tumor recurrence.

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Functional virus-specific memory T cells survey glioblastoma

Cited by 21 publications

References 46 publications

CD39 is expressed on functional effector and tissue resident memory CD8+ T cells

CD39 is expressed on functional effector and tissue resident memory CD8+ T cells

Antigen‐specific and cross‐reactive T cells in protection and disease

FGL2-targeting T cells exhibit antitumor effects on glioblastoma and recruit tumor-specific brain-resident memory T cells

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