Top

Published in:

Open Access 01-04-2020 | Head and Neck Cancer | Original Article

Digital pathology-aided assessment of tumor-infiltrating T lymphocytes in advanced stage, HPV-negative head and neck tumors

Authors: Emma J. de Ruiter, Reinout H. de Roest, Ruud H. Brakenhoff, C. René Leemans, Remco de Bree, Chris H. J. Terhaard, Stefan M. Willems

Published in: Cancer Immunology, Immunotherapy | Issue 4/2020

Abstract

Aim

This study aimed to evaluate the presence and prognostic value of tumor-infiltrating T cells in the tumor epithelium in advanced stage, HPV-negative head and neck squamous cell carcinoma (HNSCC) patients treated with primary chemoradiotherapy using digital pathology.

Methods

Pre-treatment biopsies from 80 oropharyngeal, 52 hypopharyngeal, and 29 laryngeal cancer patients were collected in a tissue microarray (TMA) and immunohistochemically stained for T-cell markers CD3, CD4, CD8, FoxP3, and PD1, and for immune checkpoint PD-L1. For each marker, the number of positive tumor-infiltrating lymphocytes (TILs) per mm² tumor epithelium was digitally quantified and correlated to overall survival (OS), disease-free survival (DFS), and locoregional control (LRC), as well as to clinicopathological characteristics. Differences in clinical outcome were estimated using Cox proportional hazard analysis and visualized using Kaplan–Meier curves.

Results

The patient cohort had a 3-year OS of 58%, with a median follow-up of 53 months. None of the T-cell markers showed a correlation with OS, DFS or LRC. A low N stage was correlated to a better prognosis (OS: HR 0.39, p = 0.0028, DFS: HR 0.34, p = < 0.001, LRC: HR 0.24, p = 0.008). High TIL counts were more often observed in PD-L1-positive tumors (p < 0.05).

Conclusion

This study showed an objective, digital pathology-aided method to assess TILs in the tumor epithelium. However, it did not provide evidence for a prognostic role of the presence of CD3 + , CD4 + , CD8 + , FoxP3 + , and PD1 + TILs in the tumor epithelium of advanced stage, HPV-negative HNSCC patients treated with primary chemoradiotherapy.

Available only for authorised users

Argiris A, Karamouzis MV, Raben D, Ferris RL (2008) Head and neck cancer. Lancet 371(9625):1695–1709. https://doi.org/10.1016/S0140-6736(08)60728-X CrossRefPubMedPubMedCentral

Ho AS, Kraus DH, Ganly I, Lee NY, Shah JP, Morris LG (2014) Decision making in the management of recurrent head and neck cancer. Head Neck 36(1):144–151. https://doi.org/10.1002/hed.23227 CrossRefPubMed

Agra IM, Filho JG, Martins EP, Kowalski LP (2010) Second salvage surgery for re-recurrent oral cavity and oropharynx carcinoma. Head Neck 32(8):997–1002. https://doi.org/10.1002/hed.21298 CrossRefPubMed

Begg AC (2012) Predicting recurrence after radiotherapy in head and neck cancer. Semin Radiat Oncol 22(2):108–118. https://doi.org/10.1016/j.semradonc.2011.12.002 CrossRefPubMed

Hadrup S, Donia M, Thor Straten P (2013) Effector CD4 and CD8 T cells and their role in the tumor microenvironment. Cancer Microenviron 6(2):123–133. https://doi.org/10.1007/s12307-012-0127-6 CrossRefPubMed

Curry JM, Sprandio J, Cognetti D, Luginbuhl A, Bar-ad V, Pribitkin E, Tuluc M (2014) Tumor microenvironment in head and neck squamous cell carcinoma. Semin Oncol 41(2):217–234. https://doi.org/10.1053/j.seminoncol.2014.03.003 CrossRefPubMed

Zhang H, Chen J (2018) Current status and future directions of cancer immunotherapy. J Cancer 9(10):1773–1781. https://doi.org/10.7150/jca.24577 CrossRefPubMedPubMedCentral

Moskovitz JM, Moy J, Seiwert TY, Ferris RL (2017) Immunotherapy for head and neck squamous cell carcinoma: a review of current and emerging therapeutic options. Oncologist 22(6):680–693. https://doi.org/10.1634/theoncologist.2016-0318 CrossRefPubMedPubMedCentral

Gooden MJ, de Bock GH, Leffers N, Daemen T, Nijman HW (2011) The prognostic influence of tumour-infiltrating lymphocytes in cancer: a systematic review with meta-analysis. Br J Cancer 105(1):93–103. https://doi.org/10.1038/bjc.2011.189 CrossRefPubMedPubMedCentral

10.

Knocke S, Fleischmann-Mundt B, Saborowski M, Manns MP, Kuhnel F, Wirth TC, Woller N (2016) Tailored tumor immunogenicity reveals regulation of CD4 and CD8 T Cell responses against cancer. Cell Rep 17(9):2234–2246. https://doi.org/10.1016/j.celrep.2016.10.086 CrossRefPubMed

11.

McIntire PJ, Irshaid L, Liu Y, Chen Z, Menken F, Nowak E, Shin SJ, Ginter PS (2018) Hot spot and whole-tumor enumeration of CD8(+) tumor-infiltrating lymphocytes utilizing digital image analysis is prognostic in triple-negative breast cancer. Clin Breast Cancer 18(6):451–458 e451. https://doi.org/10.1016/j.clbc.2018.04.019

12.

McIntire PJ, Zhong E, Patel A, Khani F, D'Alfonso T, Chen Z, Shin SJ, Ginter PS (2018) Hotspot enumeration of CD8+ tumor infiltrating lymphocyte using digital image analysis in triple negative breast Cancer yields consistent results. Hum Pathol. https://doi.org/10.1016/j.humpath.2018.10.014 CrossRefPubMed

13.

de Ruiter EJ, Ooft ML, Devriese LA, Willems SM (2017) The prognostic role of tumor infiltrating T-lymphocytes in squamous cell carcinoma of the head and neck: a systematic review and meta-analysis. Oncoimmunology 6(11):e1356148. https://doi.org/10.1080/2162402X.2017.1356148 CrossRefPubMedPubMedCentral

14.

Balermpas P, Michel Y, Wagenblast J, Seitz O, Weiss C, Rodel F, Rodel C, Fokas E (2014) Tumour-infiltrating lymphocytes predict response to definitive chemoradiotherapy in head and neck cancer. Br J Cancer 110(2):501–509. https://doi.org/10.1038/bjc.2013.640 CrossRefPubMed

15.

Nasman A, Romanitan M, Nordfors C, Grun N, Johansson H, Hammarstedt L, Marklund L, Munck-Wikland E, Dalianis T, Ramqvist T (2012) Tumor infiltrating CD8+ and Foxp3+ lymphocytes correlate to clinical outcome and human papillomavirus (HPV) status in tonsillar cancer. PLoS ONE 7(6):e38711. https://doi.org/10.1371/journal.pone.0038711 CrossRefPubMedPubMedCentral

16.

Nordfors C, Grun N, Tertipis N, Ahrlund-Richter A, Haeggblom L, Sivars L, Du J, Nyberg T, Marklund L, Munck-Wikland E, Nasman A, Ramqvist T, Dalianis T (2013) CD8+ and CD4+ tumour infiltrating lymphocytes in relation to human papillomavirus status and clinical outcome in tonsillar and base of tongue squamous cell carcinoma. Eur J Cancer 49(11):2522–2530. https://doi.org/10.1016/j.ejca.2013.03.019 CrossRefPubMed

17.

Oguejiofor K, Hall J, Slater C, Betts G, Hall G, Slevin N, Dovedi S, Stern PL, West CM (2015) Stromal infiltration of CD8 T cells is associated with improved clinical outcome in HPV-positive oropharyngeal squamous carcinoma. Br J Cancer 113(6):886–893. https://doi.org/10.1038/bjc.2015.277 CrossRefPubMedPubMedCentral

18.

Baras AS, Drake C, Liu JJ, Gandhi N, Kates M, Hoque MO, Meeker A, Hahn N, Taube JM, Schoenberg MP, Netto G, Bivalacqua TJ (2016) The ratio of CD8 to Treg tumor-infiltrating lymphocytes is associated with response to cisplatin-based neoadjuvant chemotherapy in patients with muscle invasive urothelial carcinoma of the bladder. Oncoimmunology 5(5):e1134412. https://doi.org/10.1080/2162402X.2015.1134412 CrossRefPubMedPubMedCentral

19.

Suzuki H, Chikazawa N, Tasaka T, Wada J, Yamasaki A, Kitaura Y, Sozaki M, Tanaka M, Onishi H, Morisaki T, Katano M (2010) Intratumoral CD8(+) T/FOXP3 (+) cell ratio is a predictive marker for survival in patients with colorectal cancer. Cancer Immunol Immunother 59(5):653–661. https://doi.org/10.1007/s00262-009-0781-9 CrossRefPubMed

20.

Piccirillo JF (1995) Inclusion of comorbidity in a staging system for head and neck cancer. Oncology (Will Park) 9(9):831–836 (discussion 841, 845–838)

21.

Oken MM, Creech RH, Tormey DC, Horton J, Davis TE, McFadden ET, Carbone PP (1982) Toxicity and response criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol 5(6):649–655CrossRefPubMed

22.

van Kempen PM, van Bockel L, Braunius WW, Moelans CB, van Olst M, de Jong R, Stegeman I, van Diest PJ, Grolman W, Willems SM (2014) HPV-positive oropharyngeal squamous cell carcinoma is associated with TIMP3 and CADM1 promoter hypermethylation. Cancer Med 3(5):1185–1196. https://doi.org/10.1002/cam4.313 CrossRefPubMedPubMedCentral

23.

Smeets SJ, Hesselink AT, Speel EJ, Haesevoets A, Snijders PJ, Pawlita M, Meijer CJ, Braakhuis BJ, Leemans CR, Brakenhoff RH (2007) A novel algorithm for reliable detection of human papillomavirus in paraffin embedded head and neck cancer specimen. Int J Cancer 121(11):2465–2472. https://doi.org/10.1002/ijc.22980 CrossRefPubMed

24.

Ferris RL, Blumenschein G Jr, Fayette J, Guigay J, Colevas AD, Licitra L, Harrington K, Kasper S, Vokes EE, Even C, Worden F, Saba NF, Iglesias Docampo LC, Haddad R, Rordorf T, Kiyota N, Tahara M, Monga M, Lynch M, Geese WJ, Kopit J, Shaw JW, Gillison ML (2016) Nivolumab for recurrent squamous-cell carcinoma of the head and neck. N Engl J Med 375(19):1856–1867. https://doi.org/10.1056/NEJMoa1602252 CrossRefPubMedPubMedCentral

25.

Koo TK, Li MY (2016) A guideline of selecting and reporting intraclass correlation coefficients for reliability research. J Chiropr Med 15(2):155–163. https://doi.org/10.1016/j.jcm.2016.02.012 CrossRefPubMedPubMedCentral

26.

Hanahan D, Weinberg RA (2011) Hallmarks of cancer: the next generation. Cell 144(5):646–674. https://doi.org/10.1016/j.cell.2011.02.013 CrossRefPubMed

27.

Kalyan A, Kircher S, Shah H, Mulcahy M, Benson A (2018) Updates on immunotherapy for colorectal cancer. J Gastrointest Oncol 9(1):160–169. https://doi.org/10.21037/jgo.2018.01.17 CrossRefPubMedPubMedCentral

28.

Tsiara A, Liontos M, Kaparelou M, Zakopoulou R, Bamias A, Dimopoulos MA (2018) Implementation of immunotherapy in the treatment of advanced non-small cell lung cancer (NSCLC). Ann Transl Med 6(8):144. https://doi.org/10.21037/atm.2018.02.07 CrossRefPubMedPubMedCentral

29.

Vonderheide RH, Domchek SM, Clark AS (2017) Immunotherapy for breast cancer: what are we missing? Clin Cancer Res 23(11):2640–2646. https://doi.org/10.1158/1078-0432.CCR-16-2569 CrossRefPubMedPubMedCentral

30.

Ling DC, Bakkenist CJ, Ferris RL, Clump DA (2018) Role of immunotherapy in head and neck cancer. Semin Radiat Oncol 28(1):12–16. https://doi.org/10.1016/j.semradonc.2017.08.009 CrossRefPubMed

31.

Denkert C, Loibl S, Noske A, Roller M, Muller BM, Komor M, Budczies J, Darb-Esfahani S, Kronenwett R, Hanusch C, von Torne C, Weichert W, Engels K, Solbach C, Schrader I, Dietel M, von Minckwitz G (2010) Tumor-associated lymphocytes as an independent predictor of response to neoadjuvant chemotherapy in breast cancer. J Clin Oncol 28(1):105–113. https://doi.org/10.1200/JCO.2009.23.7370 CrossRefPubMed

32.

Grabenbauer GG, Lahmer G, Distel L, Niedobitek G (2006) Tumor-infiltrating cytotoxic T cells but not regulatory T cells predict outcome in anal squamous cell carcinoma. Clin Cancer Res 12(11 Pt 1):3355–3360. https://doi.org/10.1158/1078-0432.CCR-05-2434 CrossRefPubMed

33.

Kawai O, Ishii G, Kubota K, Murata Y, Naito Y, Mizuno T, Aokage K, Saijo N, Nishiwaki Y, Gemma A, Kudoh S, Ochiai A (2008) Predominant infiltration of macrophages and CD8(+) T Cells in cancer nests is a significant predictor of survival in stage IV nonsmall cell lung cancer. Cancer 113(6):1387–1395. https://doi.org/10.1002/cncr.23712 CrossRefPubMed

34.

Bhardwaj N (2007) Harnessing the immune system to treat cancer. J Clin Invest 117(5):1130–1136. https://doi.org/10.1172/JCI32136 CrossRefPubMedPubMedCentral

35.

Lesterhuis WJ, Haanen JB, Punt CJ (2011) Cancer immunotherapy—revisited. Nat Rev Drug Discov 10(8):591–600. https://doi.org/10.1038/nrd3500 CrossRefPubMed

36.

Del CM-BP, Driver B, Morales-Rosado JA, Deavers M, Tacha D, Bernicker E, Cagle PT, Miller RA (2018) Correlation between programmed death receptor-1 expression in tumor-infiltrating lymphocytes and programmed death ligand-1 expression in non-small cell lung carcinoma. Arch Pathol Lab Med 142(11):1388–1393. https://doi.org/10.5858/arpa.2017-0516-OA CrossRef

37.

Kitano A, Ono M, Yoshida M, Noguchi E, Shimomura A, Shimoi T, Kodaira M, Yunokawa M, Yonemori K, Shimizu C, Kinoshita T, Fujiwara Y, Tsuda H, Tamura K (2017) Tumour-infiltrating lymphocytes are correlated with higher expression levels of PD-1 and PD-L1 in early breast cancer. ESMO Open 2(2):e000150. https://doi.org/10.1136/esmoopen-2016-000150 CrossRefPubMedPubMedCentral

38.

Mattox AK, Lee J, Westra WH, Pierce RH, Ghossein R, Faquin WC, Diefenbach TJ, Morris LG, Lin DT, Wirth LJ, Lefranc-Torres A, Ishida E, Chakravarty PD, Johnson L, Zeng YC, Chen H, Poznansky MC, Iyengar NM, Pai SI (2017) PD-1 expression in head and neck squamous cell carcinomas derives primarily from functionally anergic CD4(+) TILs in the presence of PD-L1(+) TAMs. Cancer Res 77(22):6365–6374. https://doi.org/10.1158/0008-5472.CAN-16-3453 CrossRefPubMedPubMedCentral

39.

Teng MW, Ngiow SF, Ribas A, Smyth MJ (2015) Classifying cancers based on T-cell infiltration and PD-L1. Cancer Res 75(11):2139–2145. https://doi.org/10.1158/0008-5472.CAN-15-0255 CrossRefPubMedPubMedCentral

40.

Mandal R, Senbabaoglu Y, Desrichard A, Havel JJ, Dalin MG, Riaz N, Lee KW, Ganly I, Hakimi AA, Chan TA, Morris LG (2016) The head and neck cancer immune landscape and its immunotherapeutic implications. JCI Insight 1(17):e89829. https://doi.org/10.1172/jci.insight.89829 CrossRefPubMedPubMedCentral

41.

Khoury T, Nagrale V, Opyrchal M, Peng X, Wang D, Yao S (2018) Prognostic significance of stromal versus intratumoral infiltrating lymphocytes in different subtypes of breast cancer treated with cytotoxic neoadjuvant chemotherapy. Appl Immunohistochem Mol Morphol 26(8):523–532. https://doi.org/10.1097/PAI.0000000000000466 CrossRefPubMedPubMedCentral

42.

Distel LV, Fickenscher R, Dietel K, Hung A, Iro H, Zenk J, Nkenke E, Buttner M, Niedobitek G, Grabenbauer GG (2009) Tumour infiltrating lymphocytes in squamous cell carcinoma of the oro- and hypopharynx: prognostic impact may depend on type of treatment and stage of disease. Oral Oncol 45(10):e167–174. https://doi.org/10.1016/j.oraloncology.2009.05.640 CrossRefPubMed

43.

Hasmim M, Badoual C, Vielh P, Drusch F, Marty V, Laplanche A, de Oliveira DM, Roussel H, De Guillebon E, Oudard S, Hans S, Tartour E, Chouaib S (2013) Expression of EPHRIN-A1, SCINDERIN and MHC class I molecules in head and neck cancers and relationship with the prognostic value of intratumoral CD8+ T cells. BMC Cancer 13:592. https://doi.org/10.1186/1471-2407-13-592 CrossRefPubMedPubMedCentral

44.

Kim HR, Ha SJ, Hong MH, Heo SJ, Koh YW, Choi EC, Kim EK, Pyo KH, Jung I, Seo D, Choi J, Cho BC, Yoon SO (2016) PD-L1 expression on immune cells, but not on tumor cells, is a favorable prognostic factor for head and neck cancer patients. Sci Rep 6:36956. https://doi.org/10.1038/srep36956 CrossRefPubMedPubMedCentral

45.

Nguyen N, Bellile E, Thomas D, McHugh J, Rozek L, Virani S, Peterson L, Carey TE, Walline H, Moyer J, Spector M, Perim D, Prince M, McLean S, Bradford CR, Taylor JM, Wolf GT, Head NSPI (2016) Tumor infiltrating lymphocytes and survival in patients with head and neck squamous cell carcinoma. Head Neck 38(7):1074–1084. https://doi.org/10.1002/hed.24406 CrossRefPubMedPubMedCentral

46.

Park K, Cho KJ, Lee M, Yoon DH, Kim SB (2013) Importance of FOXP3 in prognosis and its relationship with p16 in tonsillar squamous cell carcinoma. Anticancer Res 33(12):5667–5673PubMed

47.

Pretscher D, Distel LV, Grabenbauer GG, Wittlinger M, Buettner M, Niedobitek G (2009) Distribution of immune cells in head and neck cancer: CD8+ T-cells and CD20+ B-cells in metastatic lymph nodes are associated with favourable outcome in patients with oro- and hypopharyngeal carcinoma. BMC Cancer 9:292. https://doi.org/10.1186/1471-2407-9-292 CrossRefPubMedPubMedCentral

48.

van Kempen PM, Noorlag R, Swartz JE, Bovenschen N, Braunius WW, Vermeulen JF, Van Cann EM, Grolman W, Willems SM (2016) Oropharyngeal squamous cell carcinomas differentially express granzyme inhibitors. Cancer Immunol Immunother 65(5):575–585. https://doi.org/10.1007/s00262-016-1819-4 CrossRefPubMedPubMedCentral

49.

Wolf GT, Chepeha DB, Bellile E, Nguyen A, Thomas D, McHugh J, University of Michigan H, Neck SP (2015) Tumor infiltrating lymphocytes (TIL) and prognosis in oral cavity squamous carcinoma: a preliminary study. Oral Oncol 51(1):90–95. https://doi.org/10.1016/j.oraloncology.2014.09.006

50.

Formenti SC, Demaria S (2013) Combining radiotherapy and cancer immunotherapy: a paradigm shift. J Natl Cancer Inst 105(4):256–265. https://doi.org/10.1093/jnci/djs629 CrossRefPubMedPubMedCentral

51.

Klug F, Prakash H, Huber PE, Seibel T, Bender N, Halama N, Pfirschke C, Voss RH, Timke C, Umansky L, Klapproth K, Schakel K, Garbi N, Jager D, Weitz J, Schmitz-Winnenthal H, Hammerling GJ, Beckhove P (2013) Low-dose irradiation programs macrophage differentiation to an iNOS(+)/M1 phenotype that orchestrates effective T cell immunotherapy. Cancer Cell 24(5):589–602. https://doi.org/10.1016/j.ccr.2013.09.014 CrossRefPubMed

52.

Teng F, Mu D, Meng X, Kong L, Zhu H, Liu S, Zhang J, Yu J (2015) Tumor infiltrating lymphocytes (TILs) before and after neoadjuvant chemoradiotherapy and its clinical utility for rectal cancer. Am J Cancer Res 5(6):2064–2074PubMedPubMedCentral

53.

Homma Y, Taniguchi K, Murakami T, Nakagawa K, Nakazawa M, Matsuyama R, Mori R, Takeda K, Ueda M, Ichikawa Y, Tanaka K, Endo I (2014) Immunological impact of neoadjuvant chemoradiotherapy in patients with borderline resectable pancreatic ductal adenocarcinoma. Ann Surg Oncol 21(2):670–676. https://doi.org/10.1245/s10434-013-3390-y CrossRefPubMed

54.

Lim YJ, Koh J, Kim S, Jeon SR, Chie EK, Kim K, Kang GH, Han SW, Kim TY, Jeong SY, Park KJ, Wu HG (2017) Chemoradiation-induced alteration of programmed death-ligand 1 and CD8(+) tumor-infiltrating lymphocytes identified patients with poor prognosis in rectal cancer: a matched comparison analysis. Int J Radiat Oncol Biol Phys 99(5):1216–1224. https://doi.org/10.1016/j.ijrobp.2017.07.004 CrossRefPubMed

55.

Matsutani S, Shibutani M, Maeda K, Nagahara H, Fukuoka T, Nakao S, Hirakawa K, Ohira M (2018) Significance of tumor-infiltrating lymphocytes before and after neoadjuvant therapy for rectal cancer. Cancer Sci 109(4):966–979. https://doi.org/10.1111/cas.13542 CrossRefPubMedPubMedCentral

56.

Pelekanou V, Carvajal-Hausdorf DE, Altan M, Wasserman B, Carvajal-Hausdorf C, Wimberly H, Brown J, Lannin D, Pusztai L, Rimm DL (2017) Effect of neoadjuvant chemotherapy on tumor-infiltrating lymphocytes and PD-L1 expression in breast cancer and its clinical significance. Breast Cancer Res 19(1):91. https://doi.org/10.1186/s13058-017-0884-8 CrossRefPubMedPubMedCentral

57.

Jung AC, Guihard S, Krugell S, Ledrappier S, Brochot A, Dalstein V, Job S, de Reynies A, Noel G, Wasylyk B, Clavel C, Abecassis J (2013) CD8-alpha T-cell infiltration in human papillomavirus-related oropharyngeal carcinoma correlates with improved patient prognosis. Int J Cancer 132(2):E26–36. https://doi.org/10.1002/ijc.27776 CrossRefPubMed

58.

Ward MJ, Thirdborough SM, Mellows T, Riley C, Harris S, Suchak K, Webb A, Hampton C, Patel NN, Randall CJ, Cox HJ, Jogai S, Primrose J, Piper K, Ottensmeier CH, King EV, Thomas GJ (2014) Tumour-infiltrating lymphocytes predict for outcome in HPV-positive oropharyngeal cancer. Br J Cancer 110(2):489–500. https://doi.org/10.1038/bjc.2013.639 CrossRefPubMed

59.

Matlung SE, Wilhelmina van Kempen PM, Bovenschen N, van Baarle D, Willems SM (2016) Differences in T-cell infiltrates and survival between HPV+ and HPV- oropharyngeal squamous cell carcinoma. Future Sci OA 2(1):FSO88. https://doi.org/10.4155/fso.15.88

60.

Goethals L, Perneel C, Debucquoy A, De Schutter H, Borghys D, Ectors N, Geboes K, McBride WH, Haustermans KM (2006) A new approach to the validation of tissue microarrays. J Pathol 208(5):607–614. https://doi.org/10.1002/path.1934 CrossRefPubMed

61.

van Diest PJ (2002) No consent should be needed for using leftover body material for scientific purposes. For BMJ 325(7365):648–651CrossRefPubMed

Title: Digital pathology-aided assessment of tumor-infiltrating T lymphocytes in advanced stage, HPV-negative head and neck tumors
Authors: Emma J. de Ruiter
Reinout H. de Roest
Ruud H. Brakenhoff
C. René Leemans
Remco de Bree
Chris H. J. Terhaard
Stefan M. Willems
Publication date: 01-04-2020
Publisher: Springer Berlin Heidelberg
Keywords: Head and Neck Cancer
Pathology
Biomarkers
Published in: Cancer Immunology, Immunotherapy / Issue 4/2020
Print ISSN: 0340-7004
Electronic ISSN: 1432-0851
DOI: https://doi.org/10.1007/s00262-020-02481-3

Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras

Prof. Fabrice Barlesi

Developed by: Springer Medicine

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Aim

Methods

Results

Conclusion

Please log in to get access to this content

Other articles of this Issue 4/2020

Bovine papillomavirus prostate cancer antigen virus-like particle vaccines are efficacious in advanced cancers in the TRAMP mouse spontaneous prostate cancer model

Immune profile and immunosurveillance in treatment-naive and neoadjuvantly treated esophageal adenocarcinoma

High expression of ID1 in monocytes is strongly associated with phenotypic and functional MDSC markers in advanced melanoma

Response to ipilimumab therapy in metastatic melanoma patients: potential relevance of CTLA-4+ tumor infiltrating lymphocytes and their in situ localization

International Regensburg Center for Interventional Immunology (RCI) symposium on “Synthetic immunology and environment-adapted redirection of T cells”, 17–18 July, 2019, Regensburg, Germany

Enhanced glucose metabolism mediated by CD147 contributes to immunosuppression in hepatocellular carcinoma

Keynote webinar | Spotlight on antibody–drug conjugates in cancer