HLA-I and Cancer

Immunological and clinical significance of HLA class I antigen processing machinery component defects in malignant cells.

Concha-Benavente F1, Srivastava R2, Ferrone S3, Ferris RL4.

1. Department of Immunology, University of Pittsburgh, Pittsburgh, PA, USA.

2. Department of Otolaryngology, University of Pittsburgh, Pittsburgh, PA, USA.

3. Department of Surgery, Massachusetts General Hospital, Boston, MA, USA.

4. Department of Immunology, University of Pittsburgh, Pittsburgh, PA, USA; Department of Otolaryngology, University of Pittsburgh, Pittsburgh, PA, USA; Cancer Immunology Program, University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA. Electronic address: ferrisrl@upmc.edu.

Abstract

Experimental as well as clinical studies demonstrate that the immune system plays a major role in controlling generation and progression of tumors. The cancer immunoediting theory supports the notion that tumor cell immunogenicity is dynamically shaped by the immune system, as it eliminates immunogenic tumor cells in the early stage of the disease and then edits their antigenicity. The end result is the generation of a tumor cell population able to escape from immune recognition and elimination by tumor infiltrating lymphocytes. Two major mechanisms, which affect the target cells and the effector phase of the immune response, play a crucial role in the editing process. One is represented by the downregulation of tumor antigen (TA) processing and presentation because of abnormalities in the HLA class I antigen processing machinery (APM). The other one is represented by the anergy of effector immune infiltrates in the tumor microenvironment caused by aberrant inhibitory signals triggered by immune checkpoint receptor (ICR) ligands, such as programmed death ligand-1 (PD-L1). In this review, we will focus on tumor immune escape mechanisms caused by defects in HLA class I APM component expression and/or function in different types of cancer, with emphasis on head and neck cancer (HNC). We will also discuss the immunological implications and clinical relevance of these HLA class I APM abnormalities. Finally, we will describe strategies to counteract defective TA presentation with the expectation that they will enhance tumor recognition and elimination by tumor infiltrating effector T cells.

Oral Oncol. 2016 Jul;58:52-8. doi: 10.1016/j.oraloncology.2016.05.008. Epub 2016 Jun 2.

http://www.sciencedirect.com/science/article/pii/S1368837516300549

Md. PhD. Fernando Concha. Ex-miembro del GII

Vacunas HPV y Cancer de Cabeza y Cuello

Intra-cheek immunization as a novel vaccination route for therapeutic vaccines of head and neck squamous cell carcinomas using plasmo virus-like particles.

Macedo R1, Rochefort J2, Guillot-Delost M1, Tanaka K1, Le Moignic A1, Noizat C1, Baillou C1, Mateo V1, Carpentier AF3, Tartour E4, Bertolus C5, Bellier B6, Lescaille G2, Lemoine FM7.

1. Sorbonne Universités, UPMC/Paris 06, UMR-S INSERM U1135, CNRS ERL 8255, Center d'Immunologie et Maladies Infectieuses (CIMI-Paris) , Paris, France.

2. Sorbonne Universités, UPMC/Paris 06, UMR-S INSERM U1135, CNRS ERL 8255, Center d'Immunologie et Maladies Infectieuses (CIMI-Paris), Paris, France; Paris Diderot/Paris 07, Sorbonne Paris Cité, Assistance Publique-Hôpitaux de Paris (AP-HP), Groupe hospitalier Pitié-Salpêtrière, Department of Odontology, Paris, France.

3. Université Paris 13, AP-HP, Hôpital Avicenne, Department of Neurology, Bobigny, France.

4. Paris Descartes/Paris 05, Sorbonne Paris Cité, INSERM U970, Paris-Cardiovascular Research Center (PARC), AP-HP, Hôpital Européen Georges Pompidou, Service d'Immunologie Biologique , Paris, France.

5. Sorbonne Universités, UPMC/Paris 06, UMR-S INSERM U1135, CNRS ERL 8255, Center d'Immunologie et Maladies Infectieuses (CIMI-Paris), Paris, France; Sorbonne Universités, UPMC Univ-Paris 06, AP-HP, Groupe hospitalier Pitié-Salpêtrière, Department of Maxillofacial Surgery, Paris, France.

6. Sorbonne Universités, UPMC/Paris 06, UMR-S INSERM U959, CNRS, FRE 3632, Immunology-Immunopathology-Immunotherapy (I3), Paris, France.

7. Sorbonne Universités, UPMC/Paris 06, UMR-S INSERM U1135, CNRS ERL 8255, Center d'Immunologie et Maladies Infectieuses (CIMI-Paris), Paris, France; AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Department of Biotherapies, Paris, France.

Abstract

Despite current therapy, head and neck squamous cell carcinomas (HNSCCs) arising from various mucosal sites of the upper aero-digestive tract frequently relapse in a loco-regional manner and have a poor prognosis. Our objective was to validate an innovative mucosal route of vaccination using plasmo virus-like particles (pVLPs) in a pre-clinical orthotopic model of HNSCCs. For this purpose, we used pVLP-E7, that are plasmid DNA encoding retroviral virus-like particles carrying a truncated E7 oncoprotein from HPV-16 as antigen model, to vaccinate mice bearing pre-established TC-1 tumors implanted into the buccal mucosa. pVLP-E7 were combined with clinical grade TLR agonists (Imiquimod and CpG-ODN). In this pre-clinical orthotopic model, whose tumor microenvironment resembles to those of human HNSCCs, different mucosal vaccination routes were tested for their ability to elicit efficient immune and antitumoral responses. Results showed that mucosal intra-cheek (IC) vaccinations using pVLP-E7, comparatively to intradermic vaccinations (ID), gave rise to higher mobilization of mucosal (CD49a(+)) CD8(+) specific effector T cells in both tumor draining lymph nodes (TdLNs) and tumor microenvironment resulting in better antitumor effects and in a long-term protection against tumor rechallenge. In vivo CD8(+) depletion demonstrated that antitumoral effects were fully dependent upon the presence of CD8(+) T cells. Validation of IC mucosal vaccinations with pVLPs combined with adjuvants using a pre-clinical orthotopic model of HNSCC provides valuable pre-clinical data to rapidly envision the use of such therapeutic vaccines in patients with HNSCCs, inasmuch as vaccinal components and adjuvants can be easily obtained as clinical grade reagents.

Oncoimmunology. 2016 Jul 6;5(7):e1164363. doi: 10.1080/2162402X.2016.1164363. eCollection 2016.

http://www.tandfonline.com/doi/abs/10.1080/2162402X.2016.1164363?journalCode=koni20

Md. PhD. Rodney Macedo. Past-president del GII.