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We are analyzing https://www.nature.com/articles/s41591-021-01398-3.

Title:
An ex vivo tumor fragment platform to dissect response to PD-1 blockade in cancer | Nature Medicine
Description:
Inhibitors of the PD-1–PD-L1 axis have been approved as therapy for many human cancers. In spite of the evidence for their widespread clinical activity, little is known about the immunological alterations that occur in human cancer tissue after PD-1 blockade. We developed and employed a patient-derived tumor fragment platform to dissect the early immunological response of human tumor tissue to ex vivo PD-1 blockade. We observed that the capacity of immune cells to be reactivated ex vivo was predictive of clinical response, and perturbation analyses identified tumor-resident T cells as a key component of this immunological response. In addition, through combined analysis of baseline properties and immune response capacity, we identified a new subgroup of infiltrated tumors that lacks the capacity to respond to PD-1 blockade. Finally, the baseline presence of tertiary lymphoid structures and their components correlated with the capacity of cancers to undergo intratumoral immune cell reactivation. An ex vivo platform of patient-derived tumor fragments enables the assessment of intratumoral immune reactivation after PD-1 blockade that is predictive of clinical outcomes in patients with cancer.
Website Age:
30 years and 10 months (reg. 1994-08-11).

Matching Content Categories {📚}

  • Science
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  • Telecommunications

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Custom-built

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🌠 Phenomenal Traffic: 5M - 10M visitors per month


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Keywords {🔍}

pubmed, article, google, scholar, cas, cells, data, nature, tumor, cell, cancer, central, blockade, response, nat, immune, tumors, antipd, fig, flow, treated, extended, pdtf, pdtfs, untreated, vivo, immunotherapy, expression, netherlands, human, access, med, depicted, clinical, checkpoint, lung, supplementary, cultures, culture, analysis, melanoma, amsterdam, activation, pdtfr, content, information, change, thommen, tissue, infiltrated,

Topics {✒️}

permissions reprints nature portfolio journals received research funding privacy policy nature portfolio research support advertising social media anti-pd-l1 antibody mpdl3280a tools nki-avl core facility middle nki-avl biobank material high-definition spatial transcriptomics pd-1/pd-l1 inhibitors pd-l1/b7h-1 inhibits tertiary lymphoid structures t-cell clonal dynamics kruskal-wallis test corrected pd-1−cd8+ tumor-infiltrating immunotherapy-naïve melanoma patients pd-1–pd-l1 axis measuring genome-wide expression high-risk resectable melanoma anti-pd-1 treated fragment nature+ nature 579 nature 515 nature 406 nature 545 nature 577 nature intratumoral tcf1+pd-1+cd8+ ifnγ-induced gene expression sensitize anti-pd1 therapy cd103+ tumor-resident cd8+ anti-cd3/anti-cd28 permissions springerlink instant access cytokine/chemokine measurements performed tissue-resident memory cd8+ vivo anti-pd-1 treatment clinical development anti-pd-1 treated condition tumor-infiltrating lymphocytes author correspondence immune-checkpoint inhibitors anti-pd-1 treated pdtfs intratumoral tcr repertoire high spatial resolution

Schema {🗺️}

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      headline:An ex vivo tumor fragment platform to dissect response to PD-1 blockade in cancer
      description:Inhibitors of the PD-1–PD-L1 axis have been approved as therapy for many human cancers. In spite of the evidence for their widespread clinical activity, little is known about the immunological alterations that occur in human cancer tissue after PD-1 blockade. We developed and employed a patient-derived tumor fragment platform to dissect the early immunological response of human tumor tissue to ex vivo PD-1 blockade. We observed that the capacity of immune cells to be reactivated ex vivo was predictive of clinical response, and perturbation analyses identified tumor-resident T cells as a key component of this immunological response. In addition, through combined analysis of baseline properties and immune response capacity, we identified a new subgroup of infiltrated tumors that lacks the capacity to respond to PD-1 blockade. Finally, the baseline presence of tertiary lymphoid structures and their components correlated with the capacity of cancers to undergo intratumoral immune cell reactivation. An ex vivo platform of patient-derived tumor fragments enables the assessment of intratumoral immune reactivation after PD-1 blockade that is predictive of clinical outcomes in patients with cancer.
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