Tumor and Microenvironment Evolution during Immunotherapy with Nivolumab

Riaz, Nadeem; Havel, Jonathan J.; Makarov, Vladimir; Desrichard, Alexis; Urba, Walter J.; Sims, Jennifer S.; Hodi, F. Stephen; Martín‐Algarra, Salvador; Mandal, Rajarsi; Sharfman, William H.; Bhatia, Shailender; Hwu, Wen-Jen; Gajewski, Thomas F.; Slingluff, Craig L.; Chowell, Diego; Kendall, Sviatoslav M.; Chang, Han; Shah, Rachna; Kuo, Fengshen; Morris, Luc G.T.; Sidhom, John-William; Schneck, Jonathan P.; Horak, Christine E.; Weinhold, Nils; Chan, Timothy A.

doi:10.1016/j.cell.2017.09.028

Cell

2017

DOI: 10.1016/j.cell.2017.09.028

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Tumor and Microenvironment Evolution during Immunotherapy with Nivolumab

Nadeem Riaz

¹

,

Jonathan J. Havel

²

,

Vladimir Makarov

³

et al.

Abstract: SUMMARY The mechanisms by which immune checkpoint blockade modulates tumor evolution during therapy are unclear. We assessed genomic changes in tumors from 68 patients with advanced melanoma, who progressed on ipilimumab or were ipilimumab-naive, before and after nivolumab initiation (CA209-038 study). Tumors were analyzed by whole-exome, transcriptome, and/or T-cell receptor (TCR) sequencing. In responding patients, mutation and neoantigen load were reduced from baseline, and analysis of intratumoral heteroge… Show more

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Cited by 2,567 publications

(2,381 citation statements)

References 76 publications

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“…We next examined the association of TMB, purity, ploidy, and heterogeneity with response stratified by prior ipilimumab therapy (Extended Data Fig 6a). Unlike prior studies 44,45 , we found no specific association of higher TMB with response in the ipilimumab-naive vs. -treated subgroup (MWW p=0.15, both). However, higher heterogeneity and lower ploidy were associated with progressors only in the ipilimumab-naive subgroup (MWW p=0.06, 0.004, respectively).…”

Section: Resultscontrasting

confidence: 99%

Integrative molecular and clinical modeling of clinical outcomes to PD1 blockade in patients with metastatic melanoma

Liu

¹

,

Schilling

²

,

Liu

³

et al. 2019

Nat Med

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Exaggerated anticipatory anxiety is common in social anxiety disorder (SAD). Neuroimaging studies have revealed altered neural activity in response to social stimuli in SAD, but fewer studies have examined neural activity during anticipation of feared social stimuli in SAD. The current study examined the time course and magnitude of activity in threat processing brain regions during speech anticipation in socially anxious individuals and healthy controls (HC). Method Participants (SAD n = 58; HC n = 16) underwent functional magnetic resonance imaging (fMRI) during which they completed a 90s control anticipation task and 90s speech anticipation task.

show abstract

“…We next examined the association of TMB, purity, ploidy, and heterogeneity with response stratified by prior ipilimumab therapy (Extended Data Fig 6a). Unlike prior studies 44,45 , we found no specific association of higher TMB with response in the ipilimumab-naive vs. -treated subgroup (MWW p=0.15, both). However, higher heterogeneity and lower ploidy were associated with progressors only in the ipilimumab-naive subgroup (MWW p=0.06, 0.004, respectively).…”

Section: Resultscontrasting

confidence: 99%

Integrative molecular and clinical modeling of clinical outcomes to PD1 blockade in patients with metastatic melanoma

Liu

¹

,

Schilling

²

,

Liu

³

et al. 2019

Nat Med

Get access via publisher Add to dashboard Cite

Exaggerated anticipatory anxiety is common in social anxiety disorder (SAD). Neuroimaging studies have revealed altered neural activity in response to social stimuli in SAD, but fewer studies have examined neural activity during anticipation of feared social stimuli in SAD. The current study examined the time course and magnitude of activity in threat processing brain regions during speech anticipation in socially anxious individuals and healthy controls (HC). Method Participants (SAD n = 58; HC n = 16) underwent functional magnetic resonance imaging (fMRI) during which they completed a 90s control anticipation task and 90s speech anticipation task.

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“…These trends are visualized in the patient-level melanogenesis gene expression profiles shown in Figure S14. Despite previous reports suggesting that active melanogenesis may contribute to immune evasion and therapy resistance through immunosuppressive microenvironments [ [40] , [41] , [42] ], our data does not show a consistent association between melanogenesis activation and clinical outcomes. For example, patient P4 exhibited higher melanogenesis activity and longer survival than P2, despite both receiving immunotherapy; however, this may also be influenced by BRAF V600E mutation status.…”

Section: Discussioncontrasting

confidence: 99%

In-depth patient-specific analysis of tumor heterogeneity in melanoma brain metastasis: Insights from spatial transcriptomics and multi-region bulk sequencing

Sharma

¹

,

Rájová

²

,

Mermelekas

³

et al. 2025

Translational Oncology

0

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Exaggerated anticipatory anxiety is common in social anxiety disorder (SAD). Neuroimaging studies have revealed altered neural activity in response to social stimuli in SAD, but fewer studies have examined neural activity during anticipation of feared social stimuli in SAD. The current study examined the time course and magnitude of activity in threat processing brain regions during speech anticipation in socially anxious individuals and healthy controls (HC). Method Participants (SAD n = 58; HC n = 16) underwent functional magnetic resonance imaging (fMRI) during which they completed a 90s control anticipation task and 90s speech anticipation task.

“…Our finding that clonal spreading were enhanced after anti-PD-L1 and anti-CD4 treatments seems to contradict with many previous studies on the repertoire analysis of TILs reporting an association between oligoclonal expansion and objective antitumor effects following ICIs (Dovedi et al, 2017; Riaz et al, 2017; Yusko et al, 2019; Zhang et al, 2020). However, these studies did not separate CD4 + and CD8 + TILs prior to TCR sequencing.…”

Section: Discussioncontrasting

confidence: 99%

Clonal spreading of tumor-infiltrating T cells underlies the robust antitumor immune responses

Aoki

¹

,

Tsunoda

²

,

Ogiwara

³

et al. 2022

Preprint

Get access via publisher Add to dashboard Cite

Exaggerated anticipatory anxiety is common in social anxiety disorder (SAD). Neuroimaging studies have revealed altered neural activity in response to social stimuli in SAD, but fewer studies have examined neural activity during anticipation of feared social stimuli in SAD. The current study examined the time course and magnitude of activity in threat processing brain regions during speech anticipation in socially anxious individuals and healthy controls (HC). Method Participants (SAD n = 58; HC n = 16) underwent functional magnetic resonance imaging (fMRI) during which they completed a 90s control anticipation task and 90s speech anticipation task.

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