Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Cancer Immunology, Immunotherapy
Published in: Cancer Immunology, Immunotherapy 5/2018

01-05-2018 | Original Article

PD-L1, B7-H3, and PD-1 expression in immunocompetent vs. immunosuppressed patients with cutaneous squamous cell carcinoma

Authors: Vinod Varki, Olga B. Ioffe, Soren M. Bentzen, Jon Heath, Ashley Cellini, Josephine Feliciano, Dan P. Zandberg

Published in: Cancer Immunology, Immunotherapy | Issue 5/2018

Login to get access

Abstract

Background

To characterize the expression of co-signaling molecules PD-L1, PD-1, and B7-H3 in cutaneous squamous cell carcinoma (cSCC) by immune status.

Methods

We retrospectively analyzed 66 cases of cSCC treated with surgical resection from 2012 to 2015. Immunostained tumor sections were analyzed for percent of tumor cells expressing PD-L1 (Tum-PD-L1%), B7-H3 (Tum-B7-H3%), density of peri and intratumoral CD8 T cells (CD8 density), proportion of CD8 T cells expressing PD-1 (CD8-PD-1%) and of tumor-infiltrating immune cells (TII) expressing PD-L1 (TII-PD-L1%).

Results

Of 66 cases, 42 were immunocompetent, 24 immunosuppressed (13 organ transplant, 8 HIV+, 3 other). Defining positive expression at > 5%, 26% of tumors were positive for PD-L1, 85% for B7-H3, 80% had CD8 T cells that expressed PD-1 and 55% had TII that expressed PD-L1. Tum-B7-H3% was significantly higher (median 60 vs. 28%, p = 0.025) in immunocompetent vs. immunosuppressed patients, including when factoring in cause of immunosuppression. No significant difference in Tum-PD-L1%, TII-PD-L1%, CD8 density, or CD8-PD-1% was observed. Tumors from HIV+ patients lacked PD-L1 expression, and had lower B7-H3% (median 2.5 vs. 60%, p = 0.007), and higher CD8 density (median 75% vs. 40%, p = 0.04) compared to immunocompetent patients. Higher tumor grade (Rs = 0.34, p = 0.006) and LVI (Rs = 0.61, p < 0.001) were both associated with higher Tum-PD-L1%.

Conclusion

cSCC showed expression of PD-L1 on tumor in 26% of cases, and high tumor B7-H3 expression (85%) and PD-1 expression on CD8 TILs (80%). Tumor B7-H3 expression was significantly higher in immunocompetent vs. immunosuppressed patients, largely driven by very low expression in HIV+ patients.
Appendix
Available only for authorised users
Literature
1.
Karia PS, Han J, Schmults CD (2013) Cutaneous squamous cell carcinoma: estimated incidence of disease, nodal metastasis, and deaths from disease in the United States, 2012. J Am Acad Dermatol 68:957–966CrossRefPubMed
2.
Thompson AK, Kelley BF, Prokop LJ et al (2016) Risk factors for cutaneous squamous cell carcinoma recurrence, metastasis, and disease-specific death: a systematic review and meta-analysis. JAMA Dermatol 152:419–428CrossRefPubMedPubMedCentral
3.
Lindelof B, Sigurgeirsson B, Gabel H, Stern RS (2000) Incidence of skin cancer in 5356 patients following organ transplantation. Br J Dermatol 143:513–519PubMed
4.
Bejar C, Maubec E (2014) Therapy of advanced squamous cell carcinoma of the skin. Curr Treat Options Oncol 15:302–320CrossRefPubMed
5.
Maubec E, Petrow P, Scheer-Senyarich I et al (2011) Phase II study of cetuximab as first-line single-drug therapy in patients with unresectable squamous cell carcinoma of the skin. J Clin Oncol 29:3419–3426CrossRefPubMed
6.
Chen L (2004) Co-inhibitory molecules of the B7-CD28 family in the control of T-cell immunity. Nat Rev Immunol 4:336–347CrossRefPubMed
7.
Zandberg DP, Strome SE (2014) The role of the PD-L1:PD-1 pathway in squamous cell carcinoma of the head and neck. Oral Oncol 50:627–632CrossRefPubMed
8.
Thompson RH, Gillett MD, Cheville JC et al (2004) Costimulatory B7-H1 in renal cell carcinoma patients: Indicator of tumor aggressiveness and potential therapeutic target. Proc Natl Acad Sci U S A 101:17174–17179CrossRefPubMedPubMedCentral
9.
Inman BA, Sebo TJ, Frigola X et al (2007) PD-L1 (B7-H1) expression by urothelial carcinoma of the bladder and BCG-induced granulomata: associations with localized stage progression. Cancer 109:1499–1505CrossRefPubMed
10.
Wilke CM, Wei S, Wang L et al (2011) Dual biological effects of the cytokines interleukin-10 and interferon-gamma. Cancer Immunol Immunother 60:1529–1541CrossRefPubMed
11.
Barber DL, Wherry EJ, Masopust D et al (2006) Restoring function in exhausted CD8 T cells during chronic viral infection. Nature 439:682–687CrossRefPubMed
12.
13.
Badoual C, Hans S, Merillon N et al (2013) PD-1-expressing tumor-infiltrating T cells are a favorable prognostic biomarker in HPV-associated head and neck cancer. Cancer Res 73:128–138CrossRefPubMed
14.
15.
Borghaei H, Paz-Ares L, Horn L et al (2015) Nivolumab versus docetaxel in advanced nonsquamous non-small-cell lung cancer. N Engl J Med 373:1627–1639CrossRefPubMedPubMedCentral
16.
17.
Wang L, Kang FB, Shan BE (2014) B7-H3-mediated tumor immunology: friend or foe? Int J Cancer 134:2764–2771CrossRefPubMed
18.
Fauci JM, Straughn JM Jr, Ferrone S, Buchsbaum DJ (2012) A review of B7-H3 and B7-H4 immune molecules and their role in ovarian cancer. Gynecol Oncol 127:420–425CrossRefPubMed
19.
Powderly JCG, Flaherty K, Szmulewitz RZ, Ribas A, Weber J, Loo D, Baughman J, Chen F, Moore P, Bonvini E, Vasselli J, Wiggington J, Cohen RB, Burris H, Chmielowski B (2015) Interim results of an ongoing phase I, dose escalation study of MGA271 (Enoblituzumab), an Fc-optimized Humanized Anti-B7-H3 Monoclonal Antibody, in Patients with Advanced Solid Cancer. SITC Annual Meeting November 2015. J Immunother Cancer 3(Suppl 2) (Oral Abstract)
20.
21.
Ferris RL, Blumenschein G Jr, Fayette J et al (2016) Nivolumab for recurrent squamous-cell carcinoma of the head and neck. N Engl J Med 375:1856–1867CrossRefPubMedPubMedCentral
22.
Schaper K, Kother B, Hesse K et al (2017) The pattern and clinicopathological correlates of PD-L1 expression in cutaneous squamous cell carcinoma. Br J Dermatol 176:1354–1356CrossRefPubMed
23.
Slater NA, Googe PB (2016) PD-L1 expression in cutaneous squamous cell carcinoma correlates with risk of metastasis. J Cutan Pathol 43:663–670CrossRefPubMed
24.
Nuno-Gonzalez A, Vicente-Martin FJ, Pinedo-Moraleda F, Lopez-Estebaranz JL (2012) High-risk cutaneous squamous cell carcinoma. Actas Dermosifiliogr 103:567–578CrossRefPubMed
25.
Chow LQ, Haddad R, Gupta S et al (2016) Antitumor activity of pembrolizumab in biomarker-unselected patients with recurrent and/or metastatic head and neck squamous cell carcinoma: results from the phase Ib KEYNOTE-012 expansion cohort. J Clin Oncol 34:3838–3845CrossRefPubMed
26.
Scilla KAHJ., Ioffe OB, Cellini AL, Edelman MJ, Zandberg DP, Riedel D, Feliciano JL. (2016) PD-1, PD-L1, and B7-H3 expression in Human Immunodeficiency Virus (HIV) infected patients with aerodigestive (AD) cancers (CA). ASCO Annual Meeting 2016. J Clin Oncol 34 (suppl; abstr 11607; Poster Presentation) vol 34, No 15_suppl (May 20 Supplement), 2016: 11607 2016
27.
Yanik EL, Kaunitz GJ, Cottrell TR et al (2017) Association of HIV status with local immune response to anal squamous cell carcinoma: implications for immunotherapy. JAMA Oncol 3:974–978CrossRefPubMedPubMedCentral
28.
Li W, Kashiwamura S, Ueda H et al (2007) Protection of CD8 + T cells from activation-induced cell death by IL-18. J Leukoc Biol 82:142–151CrossRefPubMed
29.
Krynitz B, Lundh Rozell B, Lindelof B (2010) Differences in the peritumoural inflammatory skin infiltrate between squamous cell carcinomas in organ transplant recipients and immunocompetent patients. Acta Derm Venereol 90:379–385CrossRefPubMed
30.
Loos M, Hedderich DM, Ottenhausen M et al (2009) Expression of the costimulatory molecule B7-H3 is associated with prolonged survival in human pancreatic cancer. BMC Cancer 9:463CrossRefPubMedPubMedCentral
31.
Sun J, Chen LJ, Zhang GB et al (2010) Clinical significance and regulation of the costimulatory molecule B7-H3 in human colorectal carcinoma. Cancer Immunol Immunother 59:1163–1171CrossRefPubMed
32.
33.
Brunner A, Hinterholzer S, Riss P et al (2012) Immunoexpression of B7-H3 in endometrial cancer: relation to tumor T-cell infiltration and prognosis. Gynecol Oncol 124:105–111CrossRefPubMed
34.
Wang L, Zhang Q, Chen W et al (2013) B7-H3 is overexpressed in patients suffering osteosarcoma and associated with tumor aggressiveness and metastasis. PLoS One 8:e70689CrossRefPubMedPubMedCentral
35.
Sun TW, Gao Q, Qiu SJ et al (2012) B7-H3 is expressed in human hepatocellular carcinoma and is associated with tumor aggressiveness and postoperative recurrence. Cancer Immunol Immunother 61:2171–2182CrossRefPubMed
36.
Brin L, Zubair AS, Brewer JD (2014) Optimal management of skin cancer in immunosuppressed patients. Am J Clin Dermatol 15:339–356CrossRefPubMed
37.
Ong M, Ibrahim AM, Bourassa-Blanchette S et al (2016) Antitumor activity of nivolumab on hemodialysis after renal allograft rejection. J Immunother Cancer 4:64CrossRefPubMedPubMedCentral
38.
39.
Spain L, Higgins R, Gopalakrishnan K et al (2016) Acute renal allograft rejection after immune checkpoint inhibitor therapy for metastatic melanoma. Ann Oncol 27:1135–1137CrossRefPubMed
40.
41.
42.
Rizvi NA, Hellmann MD, Snyder A et al (2015) Cancer immunology. Mutational landscape determines sensitivity to PD-1 blockade in non-small cell lung cancer. Science 348:124–128CrossRefPubMedPubMedCentral
43.
44.
45.
Borradori L, Sutton B, Shayesteh P, Daniels GA (2016) Rescue therapy with anti-programmed cell death protein 1 inhibitors (PD-1) of advanced cutaneous squamous cell carcinoma and basosquamous carcinoma: preliminary experience in 5 cases. Br J Dermatol 175:1382–1386CrossRefPubMed
46.
Winkler JK, Schneiderbauer R, Bender C et al (2017) Anti-PD-1 therapy in nonmelanoma skin cancer. Br J Dermatol 176:498–502CrossRefPubMed
47.
Chang AL, Kim J, Luciano R et al (2016) A case report of unresectable cutaneous squamous cell carcinoma responsive to pembrolizumab, a programmed cell death protein 1 inhibitor. JAMA Dermatol 152:106–108CrossRefPubMed
48.
Papadopoulos KP, Owonikoko TK, Johnson ML, Brana I, Gil-Martin M, Perez RP, Moreno V, Salama A, Calvo E, Yee NS, Safran H, González-Martín A, Aljumaily R, Mahadevan D, Mohan KK, Qin R, Stankevich E, Lowy I, Fury MG, Homsi J (2017) REGN2810: a fully human anti-PD-1 monoclonal antibody, for patients with unresectable locally advanced or metastatic cutaneous squamous cell carcinoma (CSCC)—initial safety and efficacy from expansion cohorts (ECs) of phase I study. ASCO Annual Meeting 2017. J Clin Oncol 35 (suppl):9503 (Oral Abstract)
Metadata
Title
PD-L1, B7-H3, and PD-1 expression in immunocompetent vs. immunosuppressed patients with cutaneous squamous cell carcinoma
Authors
Vinod Varki
Olga B. Ioffe
Soren M. Bentzen
Jon Heath
Ashley Cellini
Josephine Feliciano
Dan P. Zandberg
Publication date
01-05-2018
Publisher
Springer Berlin Heidelberg
Published in
Cancer Immunology, Immunotherapy / Issue 5/2018
Print ISSN: 0340-7004
Electronic ISSN: 1432-0851
DOI
https://doi.org/10.1007/s00262-018-2138-8

Other articles of this Issue 5/2018

Cancer Immunology, Immunotherapy 5/2018 Go to the issue

Review

Cancer immunotherapy in patients with brain metastases

Original Article

Certain BCG-reactive responses are associated with bladder cancer prognosis

Original Article

Impaired lymphocyte function in patients with hepatic malignancies after selective internal radiotherapy

Original Article

Identification of tumor-reactive B cells and systemic IgG in breast cancer based on clonal frequency in the sentinel lymph node

Original Article

Chimeric antigen receptors with human scFvs preferentially induce T cell anti-tumor activity against tumors with high B7H6 expression

Original Article

The multi-receptor inhibitor axitinib reverses tumor-induced immunosuppression and potentiates treatment with immune-modulatory antibodies in preclinical murine models
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
Image Credits