B cell signatures and tertiary lymphoid structures contribute to outcome in head and neck squamous cell carcinoma

immuneACCESS ◽  
2021 ◽  
Author(s):  
AT Ruffin ◽  
AR Cillo ◽  
T Tabib ◽  
A Liu ◽  
S Onkar ◽  
...  
2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Ayana T. Ruffin ◽  
Anthony R. Cillo ◽  
Tracy Tabib ◽  
Angen Liu ◽  
Sayali Onkar ◽  
...  

AbstractCurrent immunotherapy paradigms aim to reinvigorate CD8+ T cells, but the contribution of humoral immunity to antitumor immunity remains understudied. Here, we demonstrate that in head and neck squamous cell carcinoma (HNSCC) caused by human papillomavirus infection (HPV+), patients have transcriptional signatures of germinal center (GC) tumor infiltrating B cells (TIL-Bs) and spatial organization of immune cells consistent with tertiary lymphoid structures (TLS) with GCs, both of which correlate with favorable outcome. GC TIL-Bs in HPV+ HNSCC are characterized by distinct waves of gene expression consistent with dark zone, light zone and a transitional state of GC B cells. Semaphorin 4a expression is enhanced on GC TIL-Bs present in TLS of HPV+ HNSCC and during the differentiation of TIL-Bs. Our study suggests that therapeutics to enhance TIL-B responses in HNSCC should be prioritized in future studies to determine if they can complement current T cell mediated immunotherapies.


2008 ◽  
Vol 123 (10) ◽  
pp. 2354-2361 ◽  
Author(s):  
Carla M.L. van Herpen ◽  
Robbert van der Voort ◽  
Jeroen A.W.M. van der Laak ◽  
Ina S. Klasen ◽  
Aniek O. de Graaf ◽  
...  

2015 ◽  
Vol 33 (15_suppl) ◽  
pp. e22108-e22108 ◽  
Author(s):  
Sacha Rothschild ◽  
Alex Lechner ◽  
Hans Anton Schloesser ◽  
Martin Thelen ◽  
Alexander Shimabukuro-Vornhagen ◽  
...  

2021 ◽  
Author(s):  
Ching-Yun Hsieh ◽  
Ming-Yu Lien ◽  
Chen-Yuan Lin ◽  
Wen-Jyi Lo ◽  
Chung-Hung Hua ◽  
...  

Abstract BackgroundThe treatment of recurrent or metastatic head and neck squamous-cell carcinoma (R/M HNSCC) remains challenging. Preclinical studies revealed that B cell depletion could modulate the microenvironment and overcome chemoresistance. We conducted a phase I study to evaluate the feasibility and safety of B cell depletion using the anti-CD20 antibody rituximab to treat HNSCC.MethodsTen patients were enrolled into two protocols. The first four patients treated using protocol 1 received rituximab 1000 mg on days −14 and −7, followed by gemcitabine/cisplatin every 3 weeks, and rituximab was administered every 6 months thereafter. Because of disease hyperprogression, protocol 1 was amended to protocol 2, which consisted of the concomitant administration of rituximab 375 mg/m2 and gemcitabine/cisplatin every 3 weeks. Another six patients were enrolled and treated using protocol 2.ResultsThree patients treated using protocol 1 exhibited rapid disease progression, and the remaining patient could not undergo evaluation after rituximab treatment. Conversely, no unpredicted harm was observed in the six patients treated using protocol 2. Among these patients, one achieved complete response, and two had partial responses. The disease-free durations in these patients were 7.0, 6.2, and 7.1 months, respectively. Immune cell analysis revealed a higher ratio of cytotoxic T cells to regulatory T cells in responders than in non-responders.ConclusionsB cell depletion using rituximab alone in patients with HNSCC can cause hyperprogressive disease. Contrarily, the co-administration of rituximab and cisplatin/gemcitabine was feasible and safe.Trial registration:ClinicalTrials.gov Identifier: NCT04361409, 24/April/2020, retrospectively registered, https://clinicaltrials.gov/ct2/show/study/NCT04361409


2016 ◽  
Vol 46 (1) ◽  
pp. 53
Author(s):  
Azwar Azwar ◽  
Sofia Mubarika ◽  
Agus Surono

Latar belakang: Karsinoma sel skuamosa kepala dan leher merupakan salah satu kanker terseringdi seluruh dunia. Pendekatan pengobatan agresif dan multidisiplin telah dilakukan, namun belum adapeningkatan yang signifikan dalam kelangsungan hidup 5 tahun, selama 20 tahun terakhir. Kegagalanpengobatan terjadi dalam bentuk kekambuhan lokoregional, metastasis jauh, dan/atau tumor primer kedua.Berbagai penanda molekular tumor telah diteliti untuk mengetahui potensinya dalam memprediksi hasilpenyakit atau respon terhadap terapi.Tujuan: Mengetahui hubungan ekspresi protein p53, Bcl-2, c-Myc,dan MMP-9 berdasarkan gambaran klinikopatologis karsinoma sel skuamosa kepala dan leher di RumahSakit dr. Zainoel Abidin.Metode: Studi menggunakan desain cross sectional. Sampel terdiri dari 60blok parafin karsinoma sel skuamosa kepala dan leher. Prosedur pewarnaan imunohistokimia dilakukandengan menggunakan antibodi monoklonal terhadap p53, Bcl-2, c-Myc, dan MMP-9. Ekspresi proteinp53, Bcl-2, c-Myc, dan MMP-9 dianalisis secara imunohistokimia pada karsinoma sel skuamosa kepaladan leher kemudian hasilnya dihubungkan dengan parameter klinikopatologis seperti usia, jenis kelamin,lokasi tumor, diferensiasi tumor, metastasis kelenjar getah bening dan stadium tumor, kemudian dianalisisstatistik dengan Chi square.Hasil: Hasil penelitian menunjukkan terdapat hubungan bermakna tingkatekspresi p53 dengan metastasis lokal (p=0,021) dan ada hubungan bermakna tingkat ekspresi MMP-9dengan lokasi tumor (p=0,026). Tidak terdapat hubungan ekspresi p53, Bcl-2, cMyc, dan MMP-9 terhadapusia, jenis kelamin, stadium tumor, diferensiasi histologi, tingkat T, N, dan metastasis jauh.Kesimpulan:Ada hubungan ekpresi p53 dengan metastasis kelenjar limfe regional dan ekspresi MMP-9 dengan lokasitumor pada karsinoma sel skuamosa kepala dan leher. Kata kunci: Karsinoma sel skuamosa kepala dan leher, p53, Bcl-2, c-Myc, MMP-9 ABSTRACTBackground: Head and neck squamous cell carcinoma (HNSCC) is one of the most commoncancers world wide. Although aggressive and multidisciplinary approach to the treatment has been done,there is no significant improvement in 5-year survival in the last 20 years. Treatment failure occurredin the form of locoregional recurrence, distant metastasis, and/or a second primary tumor. A variety oftumor molecular markers have been studied to determine their potential in predicting disease outcome orresponse to the therapy. Purpose: To investigate correlation p53, Bcl-2, c-Myc, and MMP-9 expressionto clinicopathologic parameter in head and neck squamous cell carcinoma patient in dr. Zainoel Abidinhospital. Methods: Cross sectional design study. The sample was consisted of 60 paraffin blocks ofhead and neck squamous cell carcinoma. Procedure of immunohistochemical staining used monoclonalantibodies against p53, Bcl-2, c-Myc, and MMP-9. Expression of p53 protein, Bcl-2, c-Myc, and MMP-9were analyzed by immunohistochemistry in head and neck squamous cell carcinoma. Then, the results were linked to clinicopathologic parameters such as age, sex, tumor location, tumor differentiation,lymph node metastasis and tumor stage, and statistically analyzed with Chi square. Results: The resultsshowed there were significant correlation between p53 expression level with local metastasis (p=0,021)and significant correlation of MMP-9 expression levels with tumor location (p=0,026). There were norelationship of p53, Bcl-2, cMyc and MMP-9 expressions based on age, sex, stage tumor, histologicdifferentiation, level of T, N, and distant metastases. Conclusion: There were relationships between p53expression with local metastasis and MMP-9 expression with tumor location in head and neck squamouscell carcinoma. Keywords: Head and neck squamous cell carcinoma, p53, Bcl-2, c-Myc, MMP-9


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