Nanomaterials for modulating innate immune cells in cancer immunotherapy

Abstract

Cancer immunotherapy has been intensively investigated in both preclinical and clinical studies. Whereas chemotherapies use cytotoxic drugs to kill tumor cells, cancer immunotherapy is based on the ability of the immune system to fight cancer. Tumors are intimately associated with the immune system: they can suppress the immune response and/or control immune cells to support tumor growth. Immunotherapy has yielded promising results in clinical practice, but some patients show limited responses. This may reflect the complexities of the relationship between a tumor and the immune system. In an effort to improve the current immunotherapies, researchers have exploited nanomaterials in creating new strategies to cure tumors via modulation of the immune system in tumor tissues. Although extensive studies have examined the use of immune checkpoint-based immunotherapy, rather less work has focused on manipulating the innate immune cells. This review examines the recent approaches and challenges in the use of nanomaterials to modulate innate immune cells.

Keywords: Cancer immunotherapy; Innate immune cells; Nanomaterials; Tumor-associated macrophages.

Graphical abstract

Fig. 1

Interactions of immune cells and a tumor. In the tumor microenvironment, immune systems can function as a double-edged sword by promoting or inhibiting tumor growth. The role of immune cells can depend on the types of such cells present at the tumor tissues.

Fig. 2

Strategies for targeting TAMs in cancer immunotherapy. (A) Delivery of TAM-reprograming agents that can convert M2-type TAMs to M1 type were found to reverse the pro-tumorigenic effect of TAMs , , . (B) Dual-conjugated nanoparticles were decorated with HER-2 antibody and calreticulin. The binding of nanoparticles to HER-2expressing cancer cells induced macrophages to phagocytize the cancer cells via calreticulin recognition .

Fig. 3

Nanoformulations for modulation of MDSC. (A) Doxorubicin-loaded liposomes were decorated with T1 aptamers, which show selective binding affinities for MDSCs and cancer cells Liu, . (B) All-trans retinoic acid was entrapped in the pores of liposome coated-mesoporous silica nanoparticles together with the therapeutic agents, doxorubicin and interleukin-2. All-trans retinoic acid could suppress the differentiation of MDSCs in tumor tissues, leading to tumor inhibition Kong, .

Fig. 4

Neutrophil-mediated delivery of nanocarriers. CD11b antibody-modified gold nanoparticles were bound to neutrophils. The gold nanoparticleloaded neutrophils were recruited to stimulus-induced inflammatory tumor sites, facilitating the deep penetration of gold nanoparticles into the tumor tissues for photothermal therapy .

Fig. 5

Immunomodulator-loaded nanomaterials for the modulation of DCs. The combination of immunomodulators with a cancer vaccine (vaccine-adjuvant delivery) or photothermal therapy (endogenous vaccine) could evoke an effective DC-primed immune response.