Modulating barriers of tumor microenvironment through nanocarrier systems for improved cancer immunotherapy: a review of current status and future perspective

Abstract

Cancer immunotherapy suppresses and destroys tumors by reactivating and sustaining the tumorimmune process, and thus improving the immune response of the body to the tumor. Immunotherapeutic strategies are showing promising results in pre-clinical and clinical trials, however, tumor microenvironment (TME) is extremely immunosuppressive. Thus, their translation from labs to clinics still faces issues. Recently, nanomaterial-based strategies have been developed to modulate the TME for robust immunotherapeutic responses. The combination of nanotechnology with immunotherapy potentiates the effectiveness of immunotherapy by increasing delivery and retention, and by reducing immunomodulation toxicity. This review aims to highlight the barriers offered by TME for hindering the efficiency of immunotherapy for cancer treatment. Next, we highlight various nano-carriers based strategies for modulating those barriers for achieving better therapeutic efficacy of cancer immunotherapy with higher safety. This review will add to the body of scientific knowledge and will be a good reference material for academia and industries.

NK Cells in the Tumor Microenvironment as New Potential Players Mediating Chemotherapy Effects in Metastatic Melanoma

“…TME takes part in cancer development, proliferation and metastasis as well as immune escape and contributes to the failure of many conventional cancer therapies (53,54). Nanomedicine has been proposed as a new therapeutic strategy to modulate TME components to increase cancer chemotherapy performance (195,196).…”

Ganoderma lucidum Spore Polysaccharide Inhibits the Growth of Hepatocellular Carcinoma Cells by Altering Macrophage Polarity and Induction of Apoptosis

“…The tumor microenvironment combines chronic inflammation, low oxygen levels, nutritional deficiencies, and acidosis, creating extremely complex dynamic systems [ 16 ] that regulate tumor growth, proliferation, metastasis, and immune escape. Therefore, we think that the treatment of tumors by reducing the stress state of the tumor's internal environment and then feeding it back to the tumor cells may promote tumor cell apoptosis or autophagy [ 17 , 18 ]. Supernatant transfer of various cell cocultures in vitro has been used to mimic the tumor microenvironment [ 19 ].…”

Effect of a 2-HP-β-Cyclodextrin Formulation on the Biological Transport and Delivery of Chemotherapeutic PLGA Nanoparticles

“…1,2 Abnormal tumor blood vessels, high interstitial pressure, large tumor cell density, and dense extracellular matrix often hinder the penetration of nanomedicine into the tumor sites. [3][4][5] In tumor tissues, as new blood vessels are generated to supply excess nutrients and oxygen to cells, the permeability of tumor capillaries increases; therefore, the plasma proteins and other macromolecules leach out, causing lymphatic circulation, and thus, interstitial hydraulic pressure is elevated, 6,7 causing chaotic arrangement of capillaries and distortion of structure. 8 Also, increased levels of proteoglycan, growth factors, and hyaluronic acid in the extracellular matrix of tumors, increased collagen levels, 9 increased lysine oxidase content, and enhanced covalent cross-linking ability with collagen, 10,11 etc., cause accumulation of drugs in the marginal tissues of the tumor; the drug spreads slowly and faces difficulties to reach the central part, [12][13][14][15] which hinders drug delivery.…”