Neoadjuvant and Adjuvant Nivolumab and Lirilumab in Patients with Recurrent, Resectable Squamous Cell Carcinoma of the Head and Neck

Hanna, Glenn J.; O’Neill, Anne; Shin, Kee-Young; Wong, Kristine; Jo, Vickie Y.; Quinn, Charles T.; Cutler, Jennifer M.; Flynn, Michelle; Lizotte, Patrick H.; Annino, Donald J.; Goguen, Laura A.; Kass, Jason; Rettig, Eleni M.; Sethi, Rosh K.V.; Lorch, Jochen H.; Schoenfeld, Jonathan D.; Margalit, Danielle N.; Tishler, Roy B.; Everett, Peter C.; Desai, Anupam M.; Cavanaugh, Megan E.; Paweletz, Cloud P.; Egloff, Ann Marie; Uppaluri, Ravindra; Haddad, Robert I.

doi:10.1158/1078-0432.ccr-21-2635

Cited by 70 publications

(40 citation statements)

References 40 publications

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“…The introduction of anti-PD-1 immunotherapy allowed long-term survival in a small proportion of patients [ 5 ]. Today, anti-PD-1 immunotherapy is shifting from the palliative setting to earlier disease stages up to neoadjuvant immunotherapy, which additionally increases the response rate [ 6 , 7 ]. However, more than half of patients do not respond even to modern neoadjuvant immunotherapy protocols.…”

Section: Introductionmentioning

confidence: 99%

Beyond PD-L1—Identification of Further Potential Therapeutic Targets in Oral Cancer

Weber

Lutz

Olmos

et al. 2022

Cancers

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Background: The involvement of immune cell infiltration and immune regulation in the progression of oral squamous cell carcinoma (OSCC) is shown. Anti-PD-1 therapy is approved for the treatment of advanced OSCC cases, but not all patients respond to immune checkpoint inhibitors. Hence, further targets for therapeutic approaches are needed. The number of identified cellular receptors with immune checkpoint function is constantly increasing. This study aimed to perform a comparative analysis of a large number of immune checkpoints in OSCC in order to identify possible targets for therapeutic application. Materials and Methods: A NanoString mRNA analysis was performed to assess the expression levels of 21 immune regulatory checkpoint molecules in OSCC tissue (n = 98) and healthy oral mucosa (NOM; n = 41). The expression rates were compared between the two groups, and their association with prognostic parameters was determined. Additionally, relevant correlations between the expression levels of different checkpoints were examined. Results: In OSCC tissue, significantly increased expression of CD115, CD163, CD68, CD86, CD96, GITRL, CD28 and PD-L1 was detected. Additionally, a marginally significant increase in CD8 expression was observed. BTLA and PD-1 levels were substantially increased, but the differential expression was not statistically significant. The expression of CD137L was significantly downregulated in OSCC compared to NOM. Correlations between immune checkpoint expression levels were demonstrated, and some occurred specifically in OSCC tissue. Conclusions: The upregulation of inhibitory receptors and ligands and the downregulation of activators could contribute to reduced effector T-cell function and could induce local immunosuppression in OSCC. Increased expression of activating actors of the immune system could be explained by the increased infiltration of myeloid cells and T-cells in OSCC tissue. The analysis contributes to the understanding of immune escape in OSCC and reveals potential targets for oral cancer immunotherapy.

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Section: Introductionmentioning

confidence: 99%

Beyond PD-L1—Identification of Further Potential Therapeutic Targets in Oral Cancer

Weber

Lutz

Olmos

et al. 2022

Cancers

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“…The first monoclonal antibodies targeting NK cell IR and to be clinically tested were the anti-KIR2DL1, -KIR2DL2, and -KIR2DL3 molecule lirilumab, which blocks the inhibitory interaction of the KIR with HLA-C proteins [ 89 ], and the anti-NKG2A antibody monalizumab, interfering with the binding of the IR NKG2A, expressed by subsets of NK cells and CD8+ T lymphocytes, with its ligand HLA-E [ 90 , 91 ]. The former was recently tested in clinical trials in combination with the anti-PD-1 antibody nivolumab against hematologic [ 92 ] and solid (head and neck) tumors [ 93 ] and showed some efficiency, even in terms of disease free and overall survival [ 93 ]. Regarding monalizumab, a phase II trial revealed, in combination with the anti-epithelial growth factor receptor (EGFR) antibody cetuximab, an objective response rate of 31% in pretreated head and neck squamous cell carcinoma with tolerable side effects [ 90 ].…”

Section: Harnessing Of Autologous Nk Cellsmentioning

confidence: 99%

A Hot Topic: Cancer Immunotherapy and Natural Killer Cells

Michel

Ollert

Zimmer

2022

IJMS

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Despite significant progress in recent years, the therapeutic approach of the multiple different forms of human cancer often remains a challenge. Besides the well-established cancer surgery, radiotherapy and chemotherapy, immunotherapeutic strategies gain more and more attention, and some of them have already been successfully introduced into the clinic. Among these, immunotherapy based on natural killer (NK) cells is considered as one of the most promising options. In the present review, we will expose the different possibilities NK cells offer in this context, compare data about the theoretical background and mechanism(s) of action, report some results of clinical trials and identify several very recent trends. The pharmaceutical industry is quite interested in NK cell immunotherapy, which will benefit the speed of progress in the field.

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“…[20 ▪ ] and Hanna et al . [21 ▪ ]), with a targeted therapeutic (Merlino et al . [11 ▪▪ ,12 ▪▪ ]), or with primary tumour stereotactic body radiation therapy (SBRT) (Leidner et al [15 ▪▪ ]) are summarized in Table 1.…”

Section: Introductionmentioning

confidence: 99%

“…and Hanna et al . [21 ▪ ]). One assessed change in tumour physical measurement from the clinical, pretreatment measurements using callipers (Knochelmann et al .…”

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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Neoadjuvant and Adjuvant Nivolumab and Lirilumab in Patients with Recurrent, Resectable Squamous Cell Carcinoma of the Head and Neck

Cited by 70 publications

References 40 publications

Beyond PD-L1—Identification of Further Potential Therapeutic Targets in Oral Cancer

Beyond PD-L1—Identification of Further Potential Therapeutic Targets in Oral Cancer

A Hot Topic: Cancer Immunotherapy and Natural Killer Cells

Preoperative immunotherapy for head and neck cancers: state of art

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