New insights into the role of the immune microenvironment in breast carcinoma.

Recently, immune edition has been recognized as a new hallmark of cancer. In this respect, some clinical trials in breast cancer have reported imppressive outcomes related to laboratory immune findings, especially in the neoadjuvant and metastatic setting. Infiltration by tumor infiltrating lymphocytes (TIL) and their subtypes, tumor-associated macrophages (TAM) and myeloid-derived suppressive cells (MDSC) seem bona fide prognostic and even predictive biomarkers, that will eventually be incorporated into diagnostic and therapeutic algorithms of breast cancer. In addition, the complex interaction of costimulatory and coinhibitory molecules on the immune synapse and the different signals that they may exert represent another exciting field to explore. In this review we try to summarize and elucidate these new concepts and knowledge from a translational perspective focusing on breast cancer, paying special attention to those aspects that might have more significance in clinical practice and could be useful to design successful therapeutic strategies in the future.

Immune microenvironment in colorectal cancer: a new hallmark to change old paradigms.

Impact of immune microenvironment in prognosis of solid tumors has been extensively studied in the last few years. Specifically in colorectal carcinoma, increased knowledge of the immune events around these tumors and their relation with clinical outcomes have led to consider immune microenvironment as one of the most important prognostic factors in this disease. In this review we will summarize and update the current knowledge with respect to this intriguing and complex new hallmark of cancer, paying special attention to infiltration by T-infiltrating lymphocytes and their subtypes in colorectal cancer, as well as its eventual clinical translation in terms of long-term prognosis. Finally, we suggest some possible investigational approaches based on combinatorial strategies to trigger and boost immune reaction against tumor cells.

Tumor microenvironment and immune effects of antineoplastic therapy in lymphoproliferative syndromes.

Lymphomas represent a wide group of heterogenic diseases with different biological and clinical behavior. The underlying microenvironment-specific composition seems to play an essential role in this scenario, harboring the ability to develop successful immune responses or, on the contrary, leading to immune evasion and even promotion of tumor growth. Depending on surrounding lymphoid infiltrates, lymphomas may have different prognosis. Moreover, recent evidences have emerged that confer a significant impact of main lymphoma's treatment over microenvironment, with clinical consequences. In this review, we summarize these concepts from a pathological and clinical perspective. Also, the state of the art of lymphoma's anti-idiotype vaccine development is revised, highlighting the situations where this strategy has proven to be successful and eventual clues to obtain better results in the future.

Role of transforming growth factor beta in cancer microenvironment.

Transforming growth factor Beta (TGF-Beta) family members are polypeptidic cytokines with pleiotropic physiological properties. In relation to cancer, TGF-Beta exerts a dual tumour-suppressive and oncogenic effect, which is largely dependent on microenvironment stimuli. After activation of TGF-Beta signalling, two pathways can be activated: the canonical one through the mammalian Smad family or the non-canonical one activating, among others, the cellular mitogen-activated protein kinase (MAPK) signalling downstream, which interacts with Smad signalling. During tumorigenesis, cells of many cancer types often lose their response to the tumour-suppressive effects of TGF-Beta, which, in turn, has the opposite effect, acting as an autocrine tumour-promoting factor. In this review, we summarise the current knowledge about this intriguing cytokine, with special emphasis on its immunosuppressive actions.

Cancer and immune response: old and new evidence for future challenges.

Cancer may occur as a result of abnormal host immune system tolerance. Recent studies have confirmed the occurrence of spontaneous and induced antitumor immune responses expressed as the presence of tumor-infiltrating T cells in the tumor microenvironment in some cancer models. This finding has been recognized as a good prognostic factor in several types of tumors. Some chemotherapy agents, such as anthracyclines and gemcitabine, are effective boosters of the immune response through tumor-specific antigen overexpression after apoptotic tumor cell destruction. Other strategies, such as GM-CSF or interleukin-2, are pursued to increase immune cell availability in the tumor vicinity, and thus improve both antigen presentation and T-cell activation and proliferation. In addition, cytotoxic T lymphocyte antigen 4-blocking monoclonal antibodies enhance immune activity by prolonging T-cell activation. Strategies to stimulate the dormant immune system against tumors are varied and warrant further investigation of their applications to cancer therapy in the future.