Secretome and Immune Cell Attraction Analysis of Head and Neck Cancers

Overview

Journal Cancer Immunol Immunother

Specialties Allergy & Immunology
Oncology
Pharmacology

Date 2024 Sep 9

PMID 39249543

Authors

Tara Muijlwijk

Niels E Wondergem

Fatima Ekhlas

Naomi Remkes

Dennis N L M Nijenhuis

Lennart Fritz

Sonja H Ganzevles

Iris H C Miedema

C Rene Leemans

Jos B Poell

Ruud H Brakenhoff

Rieneke van de Ven

Affiliations

Soon will be listed here.

Abstract

Immune checkpoint inhibitors are approved for recurrent/metastatic head and neck squamous cell carcinoma (HNSCC) but the response rate is only 13-18%. For an effective antitumor immune response, trafficking of immune cells to the tumor microenvironment (TME) is essential. We aimed to better understand immune cell migration as well as the involved chemokines in HNSCC. A transwell assay was used to study immune cell migration toward TME-conditioned medium. While T cell migration was not observed, conventional dendritic cell (cDC) migration was induced by TME-conditioned media. cDC migration correlated with various proteins in the TME secretome. CCL8, CXCL5, CCL13 and CCL7 were tested in validation experiments and addition of these chemokines induced cDC migration. Using single cell RNA-sequencing, we observed expression of CCL8, CXCL5, CCL13 and CCL7 in cancer-associated fibroblasts (CAFs). Depleting fibroblasts led to reduced cDC migration. Thus CAFs, while often seen as suppressors of antitumor immunity, play a role in attracting cDCs toward the head and neck cancer TME, which might be crucial for effective antitumor immunity and response to therapies. Indeed, we found RNA expression signatures of the indicated chemokines, cDC and CAF subpopulations, to be significantly higher in baseline tumor specimen of patients with a major pathological response to pre-surgical anti-PD-1 treatment compared to non-responding patients.

References

Sung H, Ferlay J, Siegel R, Laversanne M, Soerjomataram I, Jemal A . Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021; 71(3):209-249. DOI: 10.3322/caac.21660. View

Rettig E, DSouza G . Epidemiology of head and neck cancer. Surg Oncol Clin N Am. 2015; 24(3):379-96. DOI: 10.1016/j.soc.2015.03.001. View

Barsouk A, Aluru J, Rawla P, Saginala K, Barsouk A . Epidemiology, Risk Factors, and Prevention of Head and Neck Squamous Cell Carcinoma. Med Sci (Basel). 2023; 11(2). PMC: 10304137. DOI: 10.3390/medsci11020042. View

Braakhuis B, Snijders P, Keune W, Meijer C, Ruijter-Schippers H, Leemans C . Genetic patterns in head and neck cancers that contain or lack transcriptionally active human papillomavirus. J Natl Cancer Inst. 2004; 96(13):998-1006. DOI: 10.1093/jnci/djh183. View

Ang K, Harris J, Wheeler R, Weber R, Rosenthal D, Nguyen-Tan P . Human papillomavirus and survival of patients with oropharyngeal cancer. N Engl J Med. 2010; 363(1):24-35. PMC: 2943767. DOI: 10.1056/NEJMoa0912217. View

Leemans C, Snijders P, Brakenhoff R . The molecular landscape of head and neck cancer. Nat Rev Cancer. 2018; 18(5):269-282. DOI: 10.1038/nrc.2018.11. View

Cramer J, Burtness B, Le Q, Ferris R . The changing therapeutic landscape of head and neck cancer. Nat Rev Clin Oncol. 2019; 16(11):669-683. DOI: 10.1038/s41571-019-0227-z. View

Ferris R, Blumenschein Jr G, Fayette J, Guigay J, Colevas A, Licitra L . Nivolumab for Recurrent Squamous-Cell Carcinoma of the Head and Neck. N Engl J Med. 2016; 375(19):1856-1867. PMC: 5564292. DOI: 10.1056/NEJMoa1602252. View

Mehra R, Seiwert T, Gupta S, Weiss J, Gluck I, Eder J . Efficacy and safety of pembrolizumab in recurrent/metastatic head and neck squamous cell carcinoma: pooled analyses after long-term follow-up in KEYNOTE-012. Br J Cancer. 2018; 119(2):153-159. PMC: 6048158. DOI: 10.1038/s41416-018-0131-9. View

10.

Masarwy R, Kampel L, Horowitz G, Gutfeld O, Muhanna N . Neoadjuvant PD-1/PD-L1 Inhibitors for Resectable Head and Neck Cancer: A Systematic Review and Meta-analysis. JAMA Otolaryngol Head Neck Surg. 2021; 147(10):871-878. PMC: 8414366. DOI: 10.1001/jamaoto.2021.2191. View

11.

de Visser K, Joyce J . The evolving tumor microenvironment: From cancer initiation to metastatic outgrowth. Cancer Cell. 2023; 41(3):374-403. DOI: 10.1016/j.ccell.2023.02.016. View

12.

Caligiuri G, Tuveson D . Activated fibroblasts in cancer: Perspectives and challenges. Cancer Cell. 2023; 41(3):434-449. PMC: 11022589. DOI: 10.1016/j.ccell.2023.02.015. View

13.

Mellman I, Chen D, Powles T, Turley S . The cancer-immunity cycle: Indication, genotype, and immunotype. Immunity. 2023; 56(10):2188-2205. DOI: 10.1016/j.immuni.2023.09.011. View

14.

Broz M, Binnewies M, Boldajipour B, Nelson A, Pollack J, Erle D . Dissecting the Tumor Myeloid Compartment Reveals Rare Activating Antigen-Presenting Cells Critical for T Cell Immunity. Cancer Cell. 2017; 26(6):938. DOI: 10.1016/j.ccell.2014.11.010. View

15.

Spranger S, Dai D, Horton B, Gajewski T . Tumor-Residing Batf3 Dendritic Cells Are Required for Effector T Cell Trafficking and Adoptive T Cell Therapy. Cancer Cell. 2017; 31(5):711-723.e4. PMC: 5650691. DOI: 10.1016/j.ccell.2017.04.003. View

16.

Salmon H, Idoyaga J, Rahman A, Leboeuf M, Remark R, Jordan S . Expansion and Activation of CD103(+) Dendritic Cell Progenitors at the Tumor Site Enhances Tumor Responses to Therapeutic PD-L1 and BRAF Inhibition. Immunity. 2016; 44(4):924-38. PMC: 4980762. DOI: 10.1016/j.immuni.2016.03.012. View

17.

Wondergem N, Miedema I, van de Ven R, Zwezerijnen G, de Graaf P, Karagozoglu K . Circulating T cell status and molecular imaging may predict clinical benefit of neoadjuvant PD-1 blockade in oral cancer. J Immunother Cancer. 2024; 12(7). PMC: 11268040. DOI: 10.1136/jitc-2024-009278. View

18.

Muijlwijk T, Nijenhuis D, Ganzevles S, Brink A, Ke C, Fass J . Comparative analysis of immune infiltrates in head and neck cancers across anatomical sites. J Immunother Cancer. 2024; 12(1). PMC: 10806653. DOI: 10.1136/jitc-2023-007573. View

19.

Muijlwijk T, Nijenhuis D, Ganzevles S, Ekhlas F, Ballesteros-Merino C, Peferoen L . Immune cell topography of head and neck cancer. J Immunother Cancer. 2024; 12(7). PMC: 11284952. DOI: 10.1136/jitc-2024-009550. View

20.

Peng Y, Xiao L, Rong H, Ou Z, Cai T, Liu N . Single-cell profiling of tumor-infiltrating TCF1/TCF7 T cells reveals a T lymphocyte subset associated with tertiary lymphoid structures/organs and a superior prognosis in oral cancer. Oral Oncol. 2021; 119:105348. DOI: 10.1016/j.oraloncology.2021.105348. View