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Tumor-associated adipocytes (TAAs) recruit monocytes and promote their differentiation into tumor-associated macrophages (TAMs) that support tumor development. Here, TAAs are engineered to promote the polarization of TAMs to the tumor suppressive M1 phenotype. Telratolimod, a toll-like receptor 7/8 agonist, is loaded into the lipid droplets of adipocytes to be released at the tumor site upon tumor cell-triggered lipolysis. Locally administered drug-loaded adipocytes increased tumor suppressive M1 macrophages in both primary and distant tumors and suppressed tumor growth in a melanoma model. Furthermore, drug-loaded adipocytes improved CD8+ T cell-mediated immune responses within the tumor microenvironment and favored dendritic cell maturation in the tumor draining lymph nodes.

Surgery with the assistance of conventional radiotherapy, chemotherapy and immunotherapy is the basis for head and neck squamous cell carcinoma (HNSCC) treatment. However, with these treatment modalities, the recurrence and metastasis of tumors remain at a high level. Increasingly, the evidence indicates an excellent anti-tumor effect of chimeric antigen receptor T (CAR-T) cells in hematological malignancy treatment, and this novel immunotherapy has attracted researchers' attention in HNSCC treatment. Although several clinical trials have been conducted, the weak anti-tumor effect and the side effects of CAR-T cell therapy against HNSCC are barriers to clinical translation. The limited choices of targeting proteins, the barriers of CAR-T cell infiltration into targeted tumors and short survival time in vivo should be solved. In this review, we introduce barriers of CAR-T cell therapy in HNSCC. The limitations and current promising strategies to overcome barriers in solid tumors, as well as the applications for HNSCC treatment, are covered. The perspectives of CAR-T cell therapy in future HNSCC treatment are also discussed. [ABSTRACT FROM AUTHOR]

Chimeric antigen receptor (CAR) T cells exhibit promising results for cancer immunotherapy. However, the clinical success is still restricted to certain types of blood cancers, while in solid tumors the clinical activity is modest and potential toxicities remain a concern. There are various barriers that prevent CAR T cells from combating solid tumors. Therefore, distinct strategies have been explored to augment CAR T cell proliferative capacity, persistence, and effector function. Altering the tumor microenvironment, and in particular its physiochemical properties and immunosuppressive milieu, is of great significance to facilitate CAR T cell therapy. In this article, emerging strategies implemented to overcome the barriers of CAR T cell therapy in solid tumors are reviewed. Enhancing infiltration, activation, and persistence of CAR T cells has been addressed in several preclinical models. The future development of this field to promote innovation and clinical translation is also discussed. [ABSTRACT FROM AUTHOR]