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Adequate Antigen Availability: A Key Issue for Novel Approaches to Tumor Vaccination and Tumor Immunotherapy

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Abstract

A crucial parameter for activation of the anti-tumor immune response is an adequate antigen availability (AAA) defined here as the optimal tumor antigen dose and related antigen processing and MHC-II-restricted presentation necessary to efficiently trigger tumor-specific TH cells. We will discuss two distinct experimental systems: a) a preventive anti-tumor vaccination system; b) a therapy-induced anti-tumor vaccination approach. In the first case tumor cells are rendered constitutively MHC-II+ by transfecting them with the MHC-II transcriptional activator CIITA. Here AAA is generated by the function of tumor’s newly expressed MHC-II molecules to present tumor-associated antigens to tumor-specific TH cells. In the second case, AAA is generated by treating established tumors with neovasculature-targeted TNFα. In conjuction with Melphalan, targeted TNFα delivery produces extensive areas of tumor necrosis that generate AAA capable of optimally activate tumor-specific TH cells which in turn activate CTL immune effectors. In both experimental systems tumor rejection and persistent and long-lived TH cell anti-tumor memory, responsible of defending the animals from subsequent challenges with tumor cells, are achieved. Based on these and other investigators’ results we propose that AAA is a key element for triggering adaptive immune functions resulting in subversion from a pro-tumor to an anti-tumor microenvironment, tumor rejection and acquisition of anti-tumor immune memory. Hypotheses of neuro-immune networks involved in these approaches are discussed. These considerations are important also for the comprehension of how chemotherapy and/or radiation therapies may help to block and/or to eradicate the tumor and for the construction of suitable anti-tumor vaccine strategies.

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Acknowledgments

This work was supported by the following grants to RSA: Associazione Italiana Ricerca sul Cancro “New strategies of tumor vaccination and immunotherapy based on optimized triggering of anti-tumor CD4+ T cells” (AIRC IG 8862); Italian Ministry of University and Research project PRIN “ New strategies of immunointervention against tumors” (2008-WXF7KK); Fondazione Cariplo “Cellular and molecular basis of human retroviral-dependent pathology”(2008–2230); University of Insubria “FAR 2009” and “FAR 2,010” to GT.

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The authors declare that they have no conflicts of interest.

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  1. Department of Surgical and Morphological Sciences, University of Insubria, Via Ottorino Rossi, n.9, 21100, Varese, Italy

    Roberto S. Accolla & Giovanna Tosi

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  1. Roberto S. Accolla
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Correspondence to Roberto S. Accolla.

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Accolla, R.S., Tosi, G. Adequate Antigen Availability: A Key Issue for Novel Approaches to Tumor Vaccination and Tumor Immunotherapy. J Neuroimmune Pharmacol 8, 28–36 (2013). https://doi.org/10.1007/s11481-012-9423-7

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