Innate immune mediators in cancer: between defense and resistance.

Chronic inflammation in the tumor microenvironment and evasion of the antitumor effector immune response are two of the emerging hallmarks required for oncogenesis and cancer progression. The innate immune system not only plays a critical role in perpetuating these tumor-promoting hallmarks but also in developing antitumor adaptive immune responses. Thus, understanding the dual role of the innate system in cancer immunology is required for the design of combined immunotherapy strategies able to tackle established tumors. Here, we review recent advances in the understanding of the role of cell populations and soluble components of the innate immune system in cancer, with a focus on complement, the adapter molecule Stimulator of Interferon Genes, natural killer cells, myeloid cells, and B cells.

Berraondo P ，Minute L ，Ajona D ，Corrales L ，Melero I ，Pio R ... -  《-》

Innate Immune Defense Mechanisms by Myeloid Cells That Hamper Cancer Immunotherapy.

Over the past decade, cancer immunotherapy has been steering immune responses toward cancer cell eradication. However, these immunotherapeutic approaches are hampered by the tumor-promoting nature of myeloid cells, including monocytes, macrophages, and neutrophils. Despite the arsenal of defense strategies against foreign invaders, myeloid cells succumb to the instructions of an established tumor. Interestingly, the most primordial defense responses employed by myeloid cells against pathogens, such as complement activation, antibody-dependent cell cytotoxicity and phagocytosis, actually seem to favor cancer progression. In this review, we discuss how rudimentary defense mechanisms deployed by myeloid cells can promote tumor progression.

Lebegge E ，Arnouk SM ，Bardet PMR ，Kiss M ，Raes G ，Van Ginderachter JA ... -  《Frontiers in Immunology》

Cancer-associated fibroblast-targeted strategy enhances antitumor immune responses in dendritic cell-based vaccine.

Given the close interaction between tumor cells and stromal cells in the tumor microenvironment (TME), TME-targeted strategies would be promising for developing integrated cancer immunotherapy. Cancer-associated fibroblasts (CAFs) are the dominant stromal component, playing critical roles in generation of the pro-tumorigenic TME. We focused on the immunosuppressive trait of CAFs, and systematically explored the alteration of tumor-associated immune responses by CAF-targeted therapy. C57BL/6 mice s.c. bearing syngeneic E.G7 lymphoma, LLC1 Lewis lung cancer, or B16F1 melanoma were treated with an anti-fibrotic agent, tranilast, to inhibit CAF function. The infiltration of immune suppressor cell types, including regulatory T cells and myeloid-derived suppressor cells, in the TME was effectively decreased through reduction of stromal cell-derived factor-1, prostaglandin E2 , and transforming growth factor-β. In tumor-draining lymph nodes, these immune suppressor cell types were significantly decreased, leading to activation of tumor-associated antigen-specific CD8(+) T cells. In addition, CAF-targeted therapy synergistically enhanced multiple types of systemic antitumor immune responses such as the cytotoxic CD8(+) T cell response, natural killer activity, and antitumor humoral immunity in combination with dendritic cell-based vaccines; however, the suppressive effect on tumor growth was not observed in tumor-bearing SCID mice. These data indicate that systemic antitumor immune responses by various immunologic cell types are required to bring out the efficacy of CAF-targeted therapy, and these effects are enhanced when combined with effector-stimulatory immunotherapy such as dendritic cell-based vaccines. Our mouse model provides a novel rationale with TME-targeted strategy for the development of cell-based cancer immunotherapy.

Ohshio Y ，Teramoto K ，Hanaoka J ，Tezuka N ，Itoh Y ，Asai T ，Daigo Y ，Ogasawara K ... -  《-》

[Immune system and tumors].

Despite having been much debated, it is now well established that the immune system plays an essential role in the fight against cancer. In this article, we will highlight the implication of the immune system in the control of tumor growth and describe the major components of the immune system involved in the antitumoral immune response. The immune system, while exerting pressure on tumor cells, also will play a pro-tumoral role by sculpting the immunogenicity of tumors cells as they develop. Finally, we will illustrate the numerous mechanisms of immune suppression that take place within the tumoral microenvironment which allow tumor cells to escape control from the immune system. The increasingly precise knowledge of the brakes to an effective antitumor immune response allows the development of immunotherapy strategies more and more innovating and promising of hope.

Terme M ，Tanchot C 《ANNALES DE PATHOLOGIE》

Innate immune cells in the tumor microenvironment.

The tumor immune microenvironment (TIME) is a complex ecosystem that contains adaptive and innate immune cells that have tumor-promoting and anti-tumor effects. There is still much to learn about the diversity, plasticity, and functions of innate immune cells in the TIME and their roles in determining the response to immunotherapies. Experts discuss recent advances in our understanding of their biology in cancer as well as outstanding questions and potential therapeutic avenues.

Li MO ，Wolf N ，Raulet DH ，Akkari L ，Pittet MJ ，Rodriguez PC ，Kaplan RN ，Munitz A ，Zhang Z ，Cheng S ，Bhardwaj N ... -  《-》