FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W4308380047> ?p ?o ?g. }

• W4308380047 abstract "<h3>Background</h3> Pre-operative immunotherapy results in pathologic tumor responses (pTR) for some patients with head and neck squamous cell carcinoma (HNSCC), but response mechanisms remain poorly defined.^1,2 We evaluated T cell profiles and clonal dynamics associated with pTR in a phase II trial of two doses of neoadjuvant pembrolizumab. <h3>Methods</h3> 29 patients with stage III/IV HPV-unrelated HNSCC were enrolled in a multicenter phase 2 clinical trial of anti-PD-1 antibody pembrolizumab (2 doses, Q3 weeks) as neoadjuvant immunotherapy over 5 weeks prior to surgery. pTR to PD-1 blockade was assessed based on histologic reduction of tumor cell-fraction, as previously published, with responders defined as pTR of >10%.¹ We profiled tumor-infiltrating lymphocytes (TILs) from 14 tumor biopsies from 4 Responders (Rs) and 4 Non-Responders (NRs), collected either before or after PD-1 blockade through single-cell RNA (scRNA-seq) and T-cell receptor sequencing (scTCR-seq). Quality and quantity of TILs were assessed with multiplex immunofluorescence. Data were validated via comparison with a similar cohort of 36 HNSCC patients receiving single-dose neoadjuvant pembrolizumab.¹ Results pTR was detected in surgical specimens from 15 patients (53%), with two-year overall survival (OS) and progression-free survival (PFS) rates of 92.2% (95% CI: 72.1-97.9) and 92.3% (95% CI: 72.6-98.0%), respectively. Single-cell analysis of CD8+ TILs identified 12 transcriptionally-defined clusters. The microenvironment of Rs compared to NRs showed higher pre-treatment frequencies of exhausted TILs (T_Ex-TILs) (p<0.0001, figure 1a), which were more clonally expanded and expressed a previously-defined gene signature associated with tumor-specificity.³ R T_Ex-TILs were dominated by T_TE-CTX, a subpopulation with characteristics of cytotoxicity and high expression of <i>ZNF683</i>, suggesting a tissue-resident memory (TRM) program.^4,5 Multiplex immunofluorescence of pre-treatment biopsies confirmed that Rs were more highly infiltrated with CD3+ TILs with a TRM phenotype, identified through CD103 co-expression (figure 1b).[4 6 pTR following PD-1 blockade was associated with contraction of highly cytotoxic T_TE-CTX clones and likely unleashing of their antitumor activity (figure 1c). Within this timeframe, immunotherapy response was predominantly attributable to activity of pre-existing CD8+ TIL clones, while phenotypic revival of persisting clones and clonal replacement were modest. For NRs, the baseline microenvironment exhibited a relative absence of <i>ZNF683</i>+CTX+ TILs with post-therapy accumulation of extremely exhausted clones lacking evidence of post-therapy reinvigoration. <h3>Conclusions</h3> A larger pre-treatment proportion of T_Ex-TILs retaining cytotoxic potential and a TRM signature are associated with pTR in HNSCC. Expanded T_TE-CTX clones were diminished in number after immunotherapy treatment, consistent with release of their anti-tumor activity and subsequent contraction due to antigen clearance. <h3>Acknowledgements</h3> This study was supported by the Alvin J. Siteman Cancer Center at Washington University School of Medicine and Barnes-Jewish Hospital in St. Louis, Missouri and the Clinical Trials Core. The Siteman Cancer Center is supported in part by the NCI Cancer Center. RU is funded by the National Cancer Institute, the National Institute for Dental and Craniofacial Research (NIH/NCI/NIDCR U01DE029188 and NIH/NIDCR R01DE027736) and a V Foundation Translational Research Award. Single-cell data acquisition was supported by Robert A. and Renee E. Belfer Foundation and Expect Miracles Foundation. Clinical trial support was through a Merck Investigator Studies Program award to R. Uppaluri/D.R. Adkins. <h3>Trial Registration </h3> clinicaltrials.gov unique identifier: NCT02296684 <h3>References</h3> Uppaluri R, <i>et al</i>. Neoadjuvant and adjuvant pembrolizumab in resectable locally advanced, human papillomavirus–unrelated head and neck cancer: a multicenter, phase II Trial. <i>Clin. Cancer Res</i>. 2020; <b>26</b>:5140–5152. Wise-Draper TM, <i>et al</i>. Phase II clinical trial of neoadjuvant and adjuvant pembrolizumab in resectable local-regionally advanced head and neck squamous cell carcinoma. <i>Clin Cancer Res</i>. 2022;<b>28</b>:1345–1352. Oliveira G, <i>et al</i>. Phenotype, specificity and avidity of antitumour CD8+ T cells in melanoma. <i>Nature</i> 2021;<b>596</b>, 119–125. Mackay LK, <i>et al</i>. Hobit and Blimp1 instruct a universal transcriptional program of tissue residency in lymphocytes. <i>Science (80-. )</i>. 2016; <b>352</b>:459–463. Parga-Vidal L, <i>et al</i>. Hobit identifies tissue-resident memory T cell precursors that are regulated by Eomes. <i>Sci. Immunol</i> 2021;<b>6</b>. Duhen T, <i>et al</i>. Co-expression of CD39 and CD103 identifies tumor-reactive CD8 T cells in human solid tumors. <i>Nat. Commun</i>. 2018;<b>9</b>. <h3>Ethics Approval</h3> This study was approved by the Institutional Review Boards of Dana-Farber/Harvard Cancer Center (DFCI#16-385), Washington University (#201412118) and Memorial Sloan-Kettering Cancer Center (MSKCC) (#18-379)." @default.
• W4308380047 created "2022-11-11" @default.
• W4308380047 creator A5005956102 @default.
• W4308380047 creator A5006906416 @default.
• W4308380047 creator A5008214979 @default.
• W4308380047 creator A5012365084 @default.
• W4308380047 creator A5013133259 @default.
• W4308380047 creator A5017340351 @default.
• W4308380047 creator A5018145418 @default.
• W4308380047 creator A5020913453 @default.
• W4308380047 creator A5022139249 @default.
• W4308380047 creator A5024024612 @default.
• W4308380047 creator A5024262059 @default.
• W4308380047 creator A5024647570 @default.
• W4308380047 creator A5027605173 @default.
• W4308380047 creator A5027679923 @default.
• W4308380047 creator A5035425249 @default.
• W4308380047 creator A5036875036 @default.
• W4308380047 creator A5040514240 @default.
• W4308380047 creator A5040973007 @default.
• W4308380047 creator A5046829739 @default.
• W4308380047 creator A5046944161 @default.
• W4308380047 creator A5047399091 @default.
• W4308380047 creator A5047701430 @default.
• W4308380047 creator A5052154004 @default.
• W4308380047 creator A5056573353 @default.
• W4308380047 creator A5056864178 @default.
• W4308380047 creator A5058975989 @default.
• W4308380047 creator A5064319129 @default.
• W4308380047 creator A5065102493 @default.
• W4308380047 creator A5066002385 @default.
• W4308380047 creator A5070948530 @default.
• W4308380047 creator A5072719557 @default.
• W4308380047 creator A5074062603 @default.
• W4308380047 creator A5075280020 @default.
• W4308380047 creator A5076166380 @default.
• W4308380047 creator A5080875822 @default.
• W4308380047 creator A5084443648 @default.
• W4308380047 creator A5086607419 @default.
• W4308380047 creator A5087519887 @default.
• W4308380047 date "2022-11-01" @default.
• W4308380047 modified "2023-09-26" @default.
• W4308380047 title "503 Cytotoxic revival is implicated in response to neoadjuvant PD-1 blockade for head and neck squamous cell carcinoma" @default.
• W4308380047 doi "https://doi.org/10.1136/jitc-2022-sitc2022.0503" @default.
• W4308380047 hasPublicationYear "2022" @default.
• W4308380047 type Work @default.
• W4308380047 citedByCount "0" @default.
• W4308380047 crossrefType "proceedings-article" @default.
• W4308380047 hasAuthorship W4308380047A5005956102 @default.
• W4308380047 hasAuthorship W4308380047A5006906416 @default.
• W4308380047 hasAuthorship W4308380047A5008214979 @default.
• W4308380047 hasAuthorship W4308380047A5012365084 @default.
• W4308380047 hasAuthorship W4308380047A5013133259 @default.
• W4308380047 hasAuthorship W4308380047A5017340351 @default.
• W4308380047 hasAuthorship W4308380047A5018145418 @default.
• W4308380047 hasAuthorship W4308380047A5020913453 @default.
• W4308380047 hasAuthorship W4308380047A5022139249 @default.
• W4308380047 hasAuthorship W4308380047A5024024612 @default.
• W4308380047 hasAuthorship W4308380047A5024262059 @default.
• W4308380047 hasAuthorship W4308380047A5024647570 @default.
• W4308380047 hasAuthorship W4308380047A5027605173 @default.
• W4308380047 hasAuthorship W4308380047A5027679923 @default.
• W4308380047 hasAuthorship W4308380047A5035425249 @default.
• W4308380047 hasAuthorship W4308380047A5036875036 @default.
• W4308380047 hasAuthorship W4308380047A5040514240 @default.
• W4308380047 hasAuthorship W4308380047A5040973007 @default.
• W4308380047 hasAuthorship W4308380047A5046829739 @default.
• W4308380047 hasAuthorship W4308380047A5046944161 @default.
• W4308380047 hasAuthorship W4308380047A5047399091 @default.
• W4308380047 hasAuthorship W4308380047A5047701430 @default.
• W4308380047 hasAuthorship W4308380047A5052154004 @default.
• W4308380047 hasAuthorship W4308380047A5056573353 @default.
• W4308380047 hasAuthorship W4308380047A5056864178 @default.
• W4308380047 hasAuthorship W4308380047A5058975989 @default.
• W4308380047 hasAuthorship W4308380047A5064319129 @default.
• W4308380047 hasAuthorship W4308380047A5065102493 @default.
• W4308380047 hasAuthorship W4308380047A5066002385 @default.
• W4308380047 hasAuthorship W4308380047A5070948530 @default.
• W4308380047 hasAuthorship W4308380047A5072719557 @default.
• W4308380047 hasAuthorship W4308380047A5074062603 @default.
• W4308380047 hasAuthorship W4308380047A5075280020 @default.
• W4308380047 hasAuthorship W4308380047A5076166380 @default.
• W4308380047 hasAuthorship W4308380047A5080875822 @default.
• W4308380047 hasAuthorship W4308380047A5084443648 @default.
• W4308380047 hasAuthorship W4308380047A5086607419 @default.
• W4308380047 hasAuthorship W4308380047A5087519887 @default.
• W4308380047 hasBestOaLocation W43083800471 @default.
• W4308380047 hasConcept C121608353 @default.
• W4308380047 hasConcept C126322002 @default.
• W4308380047 hasConcept C142724271 @default.
• W4308380047 hasConcept C143998085 @default.
• W4308380047 hasConcept C170493617 @default.
• W4308380047 hasConcept C2776107976 @default.
• W4308380047 hasConcept C2776530083 @default.
• W4308380047 hasConcept C2776833033 @default.
• W4308380047 hasConcept C2777701055 @default.
• W4308380047 hasConcept C2778292576 @default.
• W4308380047 hasConcept C2778326572 @default.
• W4308380047 hasConcept C2778468042 @default.
• W4308380047 hasConcept C2780057760 @default.

• next