Turning cold tumors into hot tumors: harnessing the potential of tumor immunity using nanoparticles

ABSTRACT

Introduction: Immune checkpoint inhibitors have considerably changed the landscape of oncology. However apart from world-acclaimed success stories limited to melanoma and lung cancer, many solid tumors failed to respond to immune checkpoint inhibitors due to limited immunogenicity, unfavorable tumor micro-environments (TME), lack of infiltrating T lymphocytes or increases in Tregs.

Areas covered: Combinatorial strategies are foreseen as the future of immunotherapy and using cytotoxics or modulating agents is expected to boost the efficacy of immune checkpoint inhibitors. In this respect, nanoparticles displaying unique pharmacokinetic features such as tumor targeting properties, optimal payload delivery and long-lasting interferences with TME, are promising candidates for such combinations. This review covers the basis, expectancies, limits and pitfalls of future combination between nanoparticles and immune check point inhibitors.

Expert opinion: Nanoparticles allow optimal delivery of variety of payloads in tumors while sparing healthy tissue, thus triggering immunogenic cell death. Depleting tumor stroma could further help immune cells and monoclonal antibodies to better circulate in the TME, plus immune-modulating properties of the charged cytotoxics. Finally, nanoparticles themselves present immunogenicity and antigenicity likely to boost immune response at the tumor level.

KEYWORDS:

• Immunotherapy
• nanoparticles
• drug delivery
• immunogenicity
• pharmacokinetics
• cancer

Article highlights

• Immunotherapy is currently limited by cold tumors displaying unfavorable immunogenic profile because of low mutational burden, harsh tumor microenvironment, plus possible deleterious impact of prior chemotherapy on patient’s innate immunity.

• Combinatorial therapy is seen as the future of immunotherapy, and associated treatments are all expected to turn cold tumors into hot tumors, so as to boost the efficacy of immune check-point inhibitors.

• Nanoparticles present promising features, making them particularly suitable candidates to be associated with immune check-point inhibitors.

• Improved pharmacokinetics, immunogenic properties, and ability to cargo a wide variety of anticancer drugs or immunomodulating agents provide nanoparticles with unique properties.

• Determining the optimal modality of such combination is challenging because of the multiple and complex interplays between nanoparticles, patient’s immunity, tumor microenvironment, and tumor cells.

This box summarizes key points contained in the article.

Acknowledgments

Anne Rodallec received a grant from French charity La Ligue Nationale contre le Cancer (# GB/MA/CD/Ep-1204) as part of her Ph.D. studies.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.