Response and recurrence correlates in individuals treated with neoadjuvant anti-PD-1 therapy for resectable oral cavity squamous cell carcinoma

Liu, Sixue; Knochelmann, Hannah M.; Lomeli, Shirley H.; Hong, Aayoung; Richardson, Mary S.; Yang, Zhentao; Lim, Raymond J.; Wang, Yan; Dumitras, Camelia; Krysan, Kostyantyn; Timmers, Cynthia; Romeo, Martin J.; Krieg, Carsten; O'Quinn, Elizabeth C; Horton, Joshua D.; Dubinett, Steven M.; Paulos, Chrystal M.; Neskey, David M.; Lo, Roger S.

doi:10.1016/j.xcrm.2021.100411

Cited by 27 publications

(38 citation statements)

References 64 publications

(80 reference statements)

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“…Further evidence of a potential immunotherapeutic role is provided by a strong trend towards more CD26 high tumor-infiltrating lymphocytes (TILs) being observed in patients with oral cavity squamous cell carcinoma who responded to neoadjuvant PD-1 therapy [ 2 , 3 ]. Clinical trials are now underway to evaluate the potential of CD4 + CD26 high T cells as next-generation ACT therapy in patients non-responsive to checkpoint blockade.…”

Section: Lessons Learned From Cell Therapiesmentioning

confidence: 99%

Perspectives in Immunotherapy: meeting report from the Immunotherapy Bridge, December 1st–2nd, 2021

et al. 2022

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Over the past decade, immunotherapy has become an increasingly fundamental modality in the treatment of cancer. The positive impact of immune checkpoint inhibition, especially anti-programmed death (PD)-1/PD-ligand (L)1 blockade, in patients with different cancers has focused attention on the potential for other immunotherapeutic approaches. These include inhibitors of additional immune checkpoints, adoptive cell transfer (ACT), and therapeutic vaccines. Patients with advanced cancers who previously had limited treatment options available may now benefit from immunotherapies that can offer durable responses and improved survival outcomes. However, despite this, a significant proportion of patients fail to respond to immunotherapy, especially those with less immunoresponsive cancer types, and there remains a need for new treatment strategies.The virtual Immunotherapy Bridge (December 1st–2nd, 2021), organized by the Fondazione Melanoma Onlus, Naples, Italy in collaboration with the Society for Immunotherapy of Cancer addressed several areas of current research in immunotherapy, including lessons learned from cell therapies, drivers of immune response, and trends in immunotherapy across different cancers, and these are summarised here.

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Section: Lessons Learned From Cell Therapiesmentioning

confidence: 99%

Perspectives in Immunotherapy: meeting report from the Immunotherapy Bridge, December 1st–2nd, 2021

et al. 2022

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“…[14 ▪▪ ], Knochelmann et al . [16 ▪▪ ,17 ▪ ] and Wise-Draper et al . [18 ▪▪ ]), in combination with an immunotherapeutic (Schoenfeld et al .…”

Section: Introductionmentioning

confidence: 96%

“…In addition, concerns have been raised about the impact of preoperative immunotherapy on surgery including wound healing [10]. Preoperative immunotherapy HNSCC clinical trial reports are emerging, and thus far, there have been no reports of delay of surgery or increased frequency of surgical or postoperative recovery complications [11 ▪▪ ,12 ▪▪ ,13 ▪ ,14 ▪▪ –16 ▪▪ ,17 ▪ ,18 ▪▪ ,19 ▪ –21 ▪ ]. Pembrolizumab/nivolumab treatment in the recurrent/metastatic setting has resulted in exceedingly rare events of pseudo progression, which results from enhanced tumour immune infiltration and immune activation [22].…”

Section: Introductionmentioning

confidence: 99%

“…One assessed change in tumour physical measurement from the clinical, pretreatment measurements using callipers (Knochelmann et al . [16 ▪▪ ,17 ▪ ]). Response rates using the various trial-specific definitions ranged between 5.9% in the HPV- subset of the Ferris trial [14 ▪▪ ] to 100% (Leidner et al .…”

Section: Introductionmentioning

confidence: 99%

“…[11 ▪▪ ,12 ▪▪ ] and Knochelmann et al . [16 ▪▪ ,17 ▪ ]), most reported a lack of concordance between radiologic and pathologic tumour response. Rate of clinical to pathologic downstaging was reported for four trials and ranged from 19 to 80 - 100% (Table 2).…”

Section: Introductionmentioning

confidence: 99%

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Preoperative immunotherapy for head and neck cancers: state of art

Egloff

Uppaluri

2022

Current Opinion in Oncology

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Purpose of reviewProgrammed cell death 1 (PD-l)-targeting agents have been FDA-approved for treatment of recurrent/ metastatic head and neck squamous cell carcinoma (HNSCC). Clinical studies employing these agents preoperatively for HNSCC in the definitive setting are emerging and have important implications. Recent findingsPreclinical studies demonstrate enhanced effectiveness of preoperative PD-1 targeting compared with postoperative treatment. Nine HNSCC clinical studies evaluating preoperative treatment with PD-1-targeted pembrolizumab/nivolumab alone or in combination therapy were recently reported. These studies differed by preoperative treatment type and duration and reported no surgical delays, no unexpected surgical complications and grade 3--4 immune-related adverse events consistent with the employed immunotherapeutic agent(s). Rates of major pathologic response (MPR), reduced residual viable tumour to 10% or less, ranged from 2.9--31% across eight trials without neoadjuvant radiation therapy. Higher PD-1 ligand (PD-L1) expression, increased inflammatory gene expression and enhanced immune cell tumour infiltration in baseline biopsies were associated with pathologic tumour response (pTR) in some studies. Any degree of pTR was associated with improved survival/relapse outcomes in two studies.

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Immune checkpoint CD161/LLT1‐associated immunological landscape and diagnostic value in oral squamous cell carcinoma

Hu,

Dong,

Xie

et al. 2024

The Journal of Pathology CR

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An active host adaptive response is characterized by the existence of programmed cell death protein 1 (PD‐1)+/IFN‐γ+ cytotoxic T cells and IFN‐γ‐induced PD‐L1+ tumor cells (TCs), which predicts high response rate to anti‐PD‐1/L1 therapy. Recently, CD161 and its ligand LLT1 (CLEC2D) have been identified as an emerging checkpoint for immunotherapy. Clarifying its heterogeneous clinical expression pattern and its immune landscape is a prerequisite for maximizing the response rate of CD161 blockade therapy in a specific population of oral squamous cell carcinoma (OSCC) patients. Here, we investigated the expression pattern of CD161/LLT1 and its association with major immunocytes (T cells, B cells, NK cells, and macrophages) by multiplex immunofluorescence, immunohistochemistry, and flow cytometry in 109 OSCC tissues and 102 peripheral blood samples. TCs showed higher LLT1 levels than tumor infiltrating lymphocytes (TILs), whereas CD161 was highly expressed in CD8+ T cells at the tumor front, which was decreased in paracancerous tissue. High expression of TC‐derived LLT1 (LLT1TC) conferred poor clinical outcomes, whereas higher CD161+ and LLT1+ TILs were associated with better prognosis. Meanwhile, patients with high LLT1TC showed a decreased ratio of CD8+/Foxp3+ T cells in situ, but CD161+ TILs correlated with more peripheral CD3+ T cells. Interestingly, treatment of OSCC patients with nivolumab (anti‐PD‐1) could restore tumoral CD161/LLT1 signal. Furthermore, an OSCC subgroup characterized by high LLT1+ TCs and low CD161+CD8+ T cells showed fewer peripheral T cells and a higher risk of lymph node metastasis, leading to a shorter 5‐year survival time (29%). More LLT1TC at the invasive front was another risk characteristic of exhausted T cells. In conclusion, in view of this heterogeneity, the LLT1/CD161 distribution pattern should be determined before CD161‐based immunotherapy.

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Response and recurrence correlates in individuals treated with neoadjuvant anti-PD-1 therapy for resectable oral cavity squamous cell carcinoma

Cited by 27 publications

References 64 publications

Perspectives in Immunotherapy: meeting report from the Immunotherapy Bridge, December 1st–2nd, 2021

Perspectives in Immunotherapy: meeting report from the Immunotherapy Bridge, December 1st–2nd, 2021

Preoperative immunotherapy for head and neck cancers: state of art

Immune checkpoint CD161/LLT1‐associated immunological landscape and diagnostic value in oral squamous cell carcinoma

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