Overcoming Resistance to Immunotherapy in Head and Neck Cancer Using Radiation: A Review

Overview

Journal Front Oncol

Specialty Oncology

Date 2021 Jul 19

PMID 34277390

Citations 9

Authors

Caressa Hui

Brittney Chau

Greg Gan

William Stokes

Sana D Karam

Arya Amini

Affiliations

Soon will be listed here.

Abstract

Radiation therapy remains at the center of head and neck cancer treatment. With improvements in treatment delivery, radiation therapy has become an affective ablative modality for head and neck cancers. Immune checkpoint inhibitors are now also playing a more active role both in the locally advanced and metastatic setting. With improved systemic options, local noninvasive modalities including radiation therapy are playing a critical role in overcoming resistance in head and neck cancer. The aim of this review is to describe the role of radiation therapy in modulating the tumor microenvironment and how radiation dose, fractionation and treatment field can impact the immune system and potentially effect outcomes when combined with immunotherapy. The review will encompass several common scenarios where radiation is used to improve outcomes and overcome potential resistance that may develop with immunotherapy in head and neck squamous cell carcinoma (HNSCC), including upfront locally advanced disease receiving definitive radiation and recurrent disease undergoing re-irradiation. Lastly, we will review the potential toxicities of combined therapy and future directions of their role in the management of HNSCC.

Citing Articles

Strategies to enhance the therapeutic efficacy of anti-PD-1 antibody, anti-PD-L1 antibody and anti-CTLA-4 antibody in cancer therapy.

Su X, Li J, Xu X, Ye Y, Wang C, Pang G J Transl Med. 2024; 22(1):751.

PMID: 39123227 PMC: 11316358. DOI: 10.1186/s12967-024-05552-6.

Mechanisms of Resistance and Therapeutic Perspectives in Immunotherapy for Advanced Head and Neck Cancers.

Meci A, Goyal N, Slonimsky G Cancers (Basel). 2024; 16(4).

PMID: 38398094 PMC: 10887076. DOI: 10.3390/cancers16040703.

An innovative gene expression modulating strategy by converting nucleic acids into HNC therapeutics using carrier-free nanoparticles.

Liu H, Huang Y, Li Z, Han S, Liu T, Zhao Q Front Immunol. 2024; 14:1343428.

PMID: 38274829 PMC: 10808498. DOI: 10.3389/fimmu.2023.1343428.

The Evolving Role of Stereotactic Body Radiation Therapy for Head and Neck Cancer: Where Do We Stand?.

Mohamad I, Karam I, El-Sehemy A, Abu-Gheida I, Al-Ibraheem A, Al-Assaf H Cancers (Basel). 2023; 15(20).

PMID: 37894377 PMC: 10605184. DOI: 10.3390/cancers15205010.

Combination of Pembrolizumab and Stereotactic Body Radiation Therapy in Recurrent Metastatic Penile Squamous Cell Carcinoma: A Case Study.

Kaakour D, Seyedin S, Houshyar R, Mar N Biomedicines. 2022; 10(12).

PMID: 36551787 PMC: 9775235. DOI: 10.3390/biomedicines10123033.

References

Corvo R . Evidence-based radiation oncology in head and neck squamous cell carcinoma. Radiother Oncol. 2007; 85(1):156-70. DOI: 10.1016/j.radonc.2007.04.002. View

Yao R, Wang Y, Lubet R, You M . Differentially expressed genes associated with mouse lung tumor progression. Oncogene. 2002; 21(37):5814-21. DOI: 10.1038/sj.onc.1205422. View

Khodarev N, Beckett M, Labay E, Darga T, Roizman B, Weichselbaum R . STAT1 is overexpressed in tumors selected for radioresistance and confers protection from radiation in transduced sensitive cells. Proc Natl Acad Sci U S A. 2004; 101(6):1714-9. PMC: 341831. DOI: 10.1073/pnas.0308102100. View

Wild A, Ye X, Ellsworth S, Smith J, Narang A, Garg T . The Association Between Chemoradiation-related Lymphopenia and Clinical Outcomes in Patients With Locally Advanced Pancreatic Adenocarcinoma. Am J Clin Oncol. 2013; 38(3):259-65. PMC: 3991773. DOI: 10.1097/COC.0b013e3182940ff9. View

Anderson A, Joller N, Kuchroo V . Lag-3, Tim-3, and TIGIT: Co-inhibitory Receptors with Specialized Functions in Immune Regulation. Immunity. 2016; 44(5):989-1004. PMC: 4942846. DOI: 10.1016/j.immuni.2016.05.001. View

Lee Y, Auh S, Wang Y, Burnette B, Wang Y, Meng Y . Therapeutic effects of ablative radiation on local tumor require CD8+ T cells: changing strategies for cancer treatment. Blood. 2009; 114(3):589-95. PMC: 2713472. DOI: 10.1182/blood-2009-02-206870. View

Sharabi A, Nirschl C, Kochel C, Nirschl T, Francica B, Velarde E . Stereotactic Radiation Therapy Augments Antigen-Specific PD-1-Mediated Antitumor Immune Responses via Cross-Presentation of Tumor Antigen. Cancer Immunol Res. 2014; 3(4):345-55. PMC: 4390444. DOI: 10.1158/2326-6066.CIR-14-0196. View

Gogineni E, Zhang I, Rana Z, Marrero M, Gill G, Sharma A . Quality of Life Outcomes Following Organ-Sparing SBRT in Previously Irradiated Recurrent Head and Neck Cancer. Front Oncol. 2019; 9:836. PMC: 6746961. DOI: 10.3389/fonc.2019.00836. View

Asna N, Livoff A, Batash R, Debbi R, Schaffer P, Rivkind T . Radiation therapy and immunotherapy-a potential combination in cancer treatment. Curr Oncol. 2018; 25(5):e454-e460. PMC: 6209565. DOI: 10.3747/co.25.4002. View

10.

Martin D, Balermpas P, Gollrad J, Weiss C, Valentini C, Stuschke M . RADIANCE - Radiochemotherapy with or without Durvalumab in the treatment of anal squamous cell carcinoma: A randomized multicenter phase II trial. Clin Transl Radiat Oncol. 2020; 23:43-49. PMC: 7218223. DOI: 10.1016/j.ctro.2020.04.010. View

11.

Formenti S, Demaria S . Systemic effects of local radiotherapy. Lancet Oncol. 2009; 10(7):718-26. PMC: 2782943. DOI: 10.1016/S1470-2045(09)70082-8. View

12.

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

13.

Shevtsov M, Sato H, Multhoff G, Shibata A . Novel Approaches to Improve the Efficacy of Immuno-Radiotherapy. Front Oncol. 2019; 9:156. PMC: 6433964. DOI: 10.3389/fonc.2019.00156. View

14.

Yamada Y, Bilsky M, Lovelock D, Venkatraman E, Toner S, Johnson J . High-dose, single-fraction image-guided intensity-modulated radiotherapy for metastatic spinal lesions. Int J Radiat Oncol Biol Phys. 2008; 71(2):484-90. DOI: 10.1016/j.ijrobp.2007.11.046. View

15.

Zhang B, Bowerman N, Salama J, Schmidt H, Spiotto M, Schietinger A . Induced sensitization of tumor stroma leads to eradication of established cancer by T cells. J Exp Med. 2007; 204(1):49-55. PMC: 2118433. DOI: 10.1084/jem.20062056. View

16.

Dudzinski S, Cameron B, Wang J, Rathmell J, Giorgio T, Kirschner A . Combination immunotherapy and radiotherapy causes an abscopal treatment response in a mouse model of castration resistant prostate cancer. J Immunother Cancer. 2019; 7(1):218. PMC: 6694548. DOI: 10.1186/s40425-019-0704-z. View

17.

Moher D, Liberati A, Tetzlaff J, Altman D . Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med. 2009; 6(7):e1000097. PMC: 2707599. DOI: 10.1371/journal.pmed.1000097. View

18.

Alterio D, Marvaso G, Ferrari A, Volpe S, Orecchia R, Jereczek-Fossa B . Modern radiotherapy for head and neck cancer. Semin Oncol. 2019; 46(3):233-245. DOI: 10.1053/j.seminoncol.2019.07.002. View

19.

Arnett A, Mou B, Owen D, Park S, Nelson K, Hallemeier C . Long-term Clinical Outcomes and Safety Profile of SBRT for Centrally Located NSCLC. Adv Radiat Oncol. 2019; 4(2):422-428. PMC: 6460233. DOI: 10.1016/j.adro.2019.01.002. View

20.

Weichselbaum R, Liang H, Deng L, Fu Y . Radiotherapy and immunotherapy: a beneficial liaison?. Nat Rev Clin Oncol. 2017; 14(6):365-379. DOI: 10.1038/nrclinonc.2016.211. View