Single Cell Analyses Reveal a Functionally Heterogeneous Exhausted CD8+ T Cell Subpopulation that is Correlated with Response to Checkpoint Therapy in Melanoma DOI
Kelly Mahuron, Osmaan Shahid, Prachi Sao

и другие.

Cancer Research, Год журнала: 2025, Номер 85(8), С. 1424 - 1440

Опубликована: Март 5, 2025

PD-1 pathway inhibitors have revolutionized cancer therapy. However, most patients do not durably benefit, highlighting the need for biomarkers to stratify as responders or nonresponders. Although CD8+ tumor-infiltrating lymphocytes (TIL) been associated with immune checkpoint therapy response, there is no consensus on which TIL subpopulations prognostic value. Preclinical studies focused progenitor-like exhausted T cells (TPEX) because TPEX proliferate more in response than other T-cell (TEX) subpopulations. inhibitor treatment drives differentiation into TEX populations that can mediate antitumor immunity. These data complicate ability identify prognostically important predict response. In this study, we found advanced melanoma ≥20% of TILs coexpressing and CTLA4 (termed CPHi TIL) had better objective rates survival following monotherapy those below threshold. Characterization subset using bulk single-cell RNA sequencing showed although TPEX-like were present within subset, they minority these cells. Rather, population was numerically dominated by subsets, including cycling, terminally exhausted-like, cytotoxic-like, and/or resident memory-like populations, a enriched glycolytic genes. Collectively, show correlate melanoma, but heterogeneous mix different may differentially contribute immunity blockade. Significance: The PD-1+ CTLA4+ lymphocyte correlating immunotherapy subpopulations, has implications optimizing checkpoint-based immunotherapy.

Язык: Английский

CD8+ T cells in the cancer-immunity cycle DOI Creative Commons
Josephine R. Giles, Anna-Maria Globig,

Susan M. Kaech

и другие.

Immunity, Год журнала: 2023, Номер 56(10), С. 2231 - 2253

Опубликована: Окт. 1, 2023

Язык: Английский

Процитировано

158
Helicobacter pylori and immunotherapy for gastrointestinal cancer DOI Creative Commons
Keren Jia, Chen Yang, Yi Xie

и другие.

The Innovation, Год журнала: 2024, Номер 5(2), С. 100561 - 100561

Опубликована: Янв. 8, 2024

infection is associated with the risk of gastrointestinal (GI) cancers; however, its impact on immunotherapy for GI cancers remains uncertain. In this study, we included 10,122 patients who underwent

Язык: Английский

Процитировано

24
The Multifaceted Role of Tissue-Resident Memory T Cells DOI
Susan N. Christo, Simone L. Park, Scott N. Mueller

и другие.

Annual Review of Immunology, Год журнала: 2024, Номер 42(1), С. 317 - 345

Опубликована: Июнь 28, 2024

Regionalized immune surveillance relies on the concerted efforts of diverse memory T cell populations. Of these, tissue-resident (TRM) cells are strategically positioned in barrier tissues, where they enable efficient frontline defense against infections and cancer. However, long-term persistence these has been implicated a variety immune-mediated pathologies. Consequently, modulating TRM populations represents an attractive strategy for novel vaccination therapeutic interventions tissue-based diseases. Here, we provide updated overview heterogeneity function across tissues disease states. We discuss mechanisms cell–mediated protection their potential contributions to autoimmune disorders. Finally, examine how responses might be durably boosted or dampened gain.

Язык: Английский

Процитировано

22
T Cells in Colorectal Cancer: Unravelling the Function of Different T Cell Subsets in the Tumor Microenvironment DOI Open Access

Ziwen Zheng,

Thomas Wieder, Bernhard Mauerer

и другие.

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(14), С. 11673 - 11673

Опубликована: Июль 19, 2023

Therapeutic options for metastatic colorectal cancer (mCRC) are very limited, and the prognosis using combination therapy with a chemotherapeutic drug targeted agent, e.g., epidermal growth factor receptor or tyrosine kinase, remains poor. Therefore, mCRC is associated poor median overall survival (mOS) of only 25–30 months. Current immunotherapies checkpoint inhibitor blockade (ICB) have led to substantial change in treatment several cancers, such as melanoma non-small cell lung cancer. In CRC, ICB has limited effects, except patients microsatellite instability-high (MSI-H) mismatch repair-deficient (dMMR) tumors, which comprise about 15% sporadic CRC 4% CRC. The vast majority CRCs microsatellite-stable (MSS) tumors low levels infiltrating immune cells, immunotherapy no clinical benefit so far. Immunotherapy inhibitors requires presence T cells into tumor microenvironment (TME). This makes most important effector TME, evidenced by establishment immunoscore—a method estimate patients. contains types that anti-tumorigenic, CD8+ pro-tumorigenic, regulatory (Tregs) helper 17 (Th17) cells. However, even show marked heterogeneity, they can become exhausted, enter state hyporesponsiveness dysfunctional express high molecules, targets ICB. To kill need recognition MHC class I, often downregulated on this case, population unconventional γδ overcome limitations conventional an αβT receptor. recognize antigens MHC-independent manner, thus acting bridge between innate adaptive immunity. Here, we discuss effects different subsets special emphasis possibility them CAR-T therapy. We explain exclusion possibilities enable these “cold” tumors.

Язык: Английский

Процитировано

36
CD69 is a Promising Immunotherapy and Prognosis Prediction Target in Cancer DOI Creative Commons
Yuchen Li, Yinfeng Gu, Pengyue Yang

и другие.

ImmunoTargets and Therapy, Год журнала: 2024, Номер Volume 13, С. 1 - 14

Опубликована: Янв. 1, 2024

Immunotherapy utilizing T cells that attack tumors is a promising strategy for treatment, but immune suppressive cell subsets, such as regulatory (Treg), and checkpoint molecules, including programmed death-1 (PD-1), can suppress the intensity of reaction thereby impair tumor clearance. Cluster differentiation 69 (CD69), known an early leukocyte activation marker, be used measure or marker activation. In recent years, functions CD69 in regulation Treg/Th17 (T helper 17) tissue retention have attracted considerable interest. These are related to role suppression environments (TME). this review, we first summarized current perspectives biological function demonstrated acts regulator activation, differentiation, retention, exhaustion. Then, discussed advances understanding deficiency anti-CD69 antibody administration shed light on value targeting cancer immunotherapy prognosis prediction.

Язык: Английский

Процитировано

11
Leveraging Long-Distance Singlet-Oxygen Transfer for Bienzyme-Locked Afterglow Imaging of Intratumoral Granule Enzymes DOI
Xin Wei, Cheng Xu, Penghui Cheng

и другие.

Journal of the American Chemical Society, Год журнала: 2024, Номер 146(25), С. 17393 - 17403

Опубликована: Июнь 11, 2024

Dual-locked activatable optical probes, leveraging the orthogonal effects of two biomarkers, hold great promise for specific imaging biological processes. However, their design approaches are limited to a short-distance energy or charge transfer mechanism, while signal readout relies on fluorescence, which inevitably suffers from tissue autofluorescence. Herein, we report long-distance singlet oxygen approach develop bienzyme-locked afterglow probe (BAAP) that emits long-lasting self-luminescence without real-time light excitation dynamic an intratumoral granule enzyme. Composed immuno-biomarker-activatable (1O2) donor and cancer-biomarker-activatable 1O2 acceptor, BAAP is initially nonafterglow. Only in presence both immune cancer biomarkers can be generated by activated subsequently diffuse toward resulting bright near-infrared with high signal-to-background ratio specificity Thus, allows tracking tumor-infiltrating cytotoxic T lymphocytes, enabling evaluation immunotherapy differentiation tumor local inflammation superb sensitivity specificity, unachievable single-locked probes. this study not only presents first dual-locked but also proposes new way probes via reactive species

Язык: Английский

Процитировано

11
Neutrophil-mediated hypoxia drives pathogenic CD8 T cell responses in cutaneous leishmaniasis DOI Creative Commons

Erin A. Fowler,

Camila Farias Amorim,

Klauss Mostacada

и другие.

Journal of Clinical Investigation, Год журнала: 2024, Номер 134(14)

Опубликована: Июнь 4, 2024

Cutaneous leishmaniasis caused by Leishmania parasites exhibits a wide range of clinical manifestations. Although influence disease severity, cytolytic CD8 T cell responses mediate disease. While these originate in the lymph node, we found that expression effector molecule granzyme B was restricted to lesional cells Leishmania-infected mice, suggesting local cues within inflamed skin induced function. Expression Blimp-1 (Prdm1), transcription factor necessary for differentiation, driven hypoxia skin. Hypoxia further enhanced recruitment neutrophils consumed oxygen produce reactive species and ultimately increased hypoxic state cells. Importantly, lesions from cutaneous patients exhibited signatures correlated with presence neutrophils. Thus, targeting hypoxia-driven signals support differentiation may improve prognosis leishmaniasis, as well other inflammatory diseases where contribute pathogenesis.

Язык: Английский

Процитировано

9
Next-generation combination approaches for immune checkpoint therapy DOI
Sangeeta Goswami, Kristen E. Pauken, Linghua Wang

и другие.

Nature Immunology, Год журнала: 2024, Номер 25(12), С. 2186 - 2199

Опубликована: Ноя. 25, 2024

Язык: Английский

Процитировано

9
CAR-T therapy and targeted treatments: Emerging combination strategies in solid tumors DOI
Jiahao Liu,

Xiaofei Jiao,

Ding Ma

и другие.

Med, Год журнала: 2024, Номер 5(6), С. 530 - 549

Опубликована: Март 27, 2024

Язык: Английский

Процитировано

7
Role of Exosomes in Cancer and Aptamer-Modified Exosomes as a Promising Platform for Cancer Targeted Therapy DOI Creative Commons
Yating Wu, Yue Cao, Li Chen

и другие.

Biological Procedures Online, Год журнала: 2024, Номер 26(1)

Опубликована: Май 27, 2024

Abstract Exosomes are increasingly recognized as important mediators of intercellular communication in cancer biology. can be derived from cells well cellular components tumor microenvironment. After secretion, the exosomes carrying a wide range bioactive cargos ingested by local or distant recipient cells. The released act through variety mechanisms to elicit multiple biological effects and impact most if not all hallmarks cancer. Moreover, owing their excellent biocompatibility capability being easily engineered modified, currently exploited promising platform for targeted therapy. In this review, we first summarize current knowledge roles risk etiology, initiation progression cancer, underlying molecular mechanisms. aptamer-modified exosome therapy is then briefly introduced. We also discuss future directions emerging biology perspective

Язык: Английский

Процитировано

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