Major fundamental factors hindering immune system in defense against tumor cells: The link between insufficiency of innate immune responses, metabolism, and neurotransmitters with effector immune cells disability.

Despite the major progresses in comprehending the mechanisms of tumor immunosurveillance and the role of innate and adaptive immune systems in recent years, there are still a number of obstacles hindering successful and effective immunotherapy of cancer. Such obstacles have been mainly attributed to the ability of tumors in creating a tolerant microenvironment and exploiting a plethora of immunosuppressive factors that counter effective immune responses against tumor cells. Here we represent a new insight into probable links between immune system disability with metabolism and chronic psychological stress which is beyond the other strategies recruited by tumors to thwart tumor immunosurveillance. In addition, we underscore the prominent role of improper innate immune responses as one of the underlying causes of either pro-tumorigenic capability or tumor immunosurveillance failure. However the insufficiency of stimulatory factors in immune responses is a major fact leading to tumor survival, metabolic suppression of immune cells in tumor microenvironment, as well as the negative influences of chronic stress and depression in cancer patients are important parameters amplifying disability of immune responses which have mostly been underestimated in cancer immunotherapy. Stress-related catecholamines are suggested as immunosuppressive factors. In addition, tumor cells have distinct metabolic pathways and secrete various metabolites in the tumor microenvironment which may inhibit T cells activity. We believe that simultaneous control of metabolic and psychological negative influences on the tumor immunosurveillance, along with addressing the weak aspects of innate and adaptive immune responses in cancer immunotherapy may result in more successful treatment of tumors.

Bahrambeigi S ，Sanajou D ，Shafiei-Irannejad V 《-》

The interplay between innate and adaptive immunity in cancer shapes the productivity of cancer immunosurveillance.

The immune system is a vital determinant of cancer and shapes its trajectory. Notably, the immune reaction to cancer harbors dual potential for suppressing or promoting cancer development and progression. This polarity of the immune response is determined, in part, by the character of the interplay between innate and adaptive immunity. On the one hand, the innate immune compartment is a necessary proponent of cancer immunity by supporting an immunostimulatory state that enables T cell immunosurveillance. However, in the setting of cancer, innate immune cells are commonly polarized with immune-suppressive properties and as a result, orchestrate a tolerogenic niche that interferes with the cytotoxic potential of tumor antigen-specific T cells. Here, we discuss the role of innate immunity as a positive and negative regulator of adaptive immunosurveillance; moreover, we highlight how tumor cells may skew leukocytes toward an immunosuppressive state and, as such, subvert the phenotypic plasticity of the immune compartment to advance disease progression. These observations establish the precedent for novel therapeutic strategies that aim to restore the tumor microenvironment to an immunoreactive state and, in doing so, condition and maintain the immunogenicity of tumors to yield deep and durable responses to immunotherapy.

Chang RB ，Beatty GL 《-》

OMIC signatures to understand cancer immunosurveillance and immunoediting: Melanoma and immune cells interplay in immunotherapy.

Melanoma is the deadliest form of skin cancer. Cutaneous melanomas usually originate from exposure to the mutagenic effects of ultraviolet radiation, and as such they exhibit the highest rate of somatic mutations than any other human cancer, and an extensive expression of neoantigens concurrently with a dense infiltrate of immune cells. The coexistence of high immunogenicity and high immune cell infiltration may sound contradictory for cancers carrying a gloomy outcome. However, recent studies have unveiled a variety of immunosuppressive mechanisms that often permeate the tumor microenvironment and that are responsible for tumor escaping from immunosurveillance mechanisms. Nonetheless, this particular immune profile has opened a new window of treatments based on immunotherapy that have significantly improved the clinical outcome of melanoma patients. Still, positive and complete therapy responses have been limited, and this particular cancer continues to be a major clinical challenge. The transcriptomic signatures of those patients with clinical benefit and those with progressive disease have provided a more complete picture of the universe of interactions between the tumor and the immune system. In this review, we integrate the results of the immunotherapy clinical trials to discuss a novel understanding of the mechanisms guiding cancer immunosurveillance and immunoediting. A clear notion of the cellular and molecular processes shaping how the immune system and the tumor are continuously coevolving would result in the rational design of combinatory therapies aiming to counteract the signaling pathways and cellular processes responsible for immunoescape mechanisms and provide clinical benefit to immunotherapy nonresponsive patients.

León-Letelier RA ，Bonifaz LC ，Fuentes-Pananá EM 《-》

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》

[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》