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Eosinophils have long been associated with allergy and parasitic infections. Today, they are considered as multifunctional leukocytes, which participate both in innate and adaptive immune response though the expression of various receptors and mediators. Although the tumor-associated eosinophilia is observed for a long time in many hematological and solid malignancies, with a generally good prognosis value, there is a lack of knowledge on the different mechanisms involved in this phenomenon. Moreover, the recent discovery in human eosinophils of different receptors and mediators, shared with lymphocytes and involved in anti-tumor defense, suggests that eosinophils can play a role in anti-tumoral immunity. We review in the present paper the current knowledge on epidemiology, recruitment, and mechanisms involved in the response of eosinophils toward tumors. [ABSTRACT FROM AUTHOR]

Effective cancer immunotherapy depends on the body’s ability to generate tumor antigen-presenting cells and tumor-reactive effector lymphocytes. As the most potent antigen presenting cells (APCs), dendritic cells (DCs) are capable of sensitizing T cells to new and recall antigens. Clinical trials of antigen-pulsed autologous DCs have been conducted in patients with a number of hematological and solid cancers, including malignant melanoma, lymphoma, myeloma, and non-small cell lung cancer. These studies suggest that antigen-loaded DC vaccination is a potentially safe and effective cancer therapy. However, the clinical results have been variable. Since the elderly are preferentially affected by diseases targeted by DC-directed immunotherapy, it is quite striking that few studies to date have focused on the effect of aging on DC function, a key aspect of optimal immunotherapy design in an aging population. In the present paper, we will discuss the consequences of aging on murine bone marrow-derived DC function and their use in cancer immunotherapy. [ABSTRACT FROM AUTHOR]

Innate and adaptive immune responses have many interactions that are regulated by the balance of signals initiated by a variety of activatory and inhibitory receptors. Among these, the NKG2D molecule was identified as expressed by T lymphocytes, including most CD8+ cells and a minority of CD4+ cells, designated TNK cells in this paper. Tumor cells may overexpress the stress-inducible NKG2D ligands (NKG2DLs: MICA/B, ULBPs) and the NKG2D signaling has been shown to be involved in lymphocyte-mediated anti-tumor activity. Aberrant expression of NKG2DLs by cancer cells, such as the release of soluble form of NKG2DLs, can lead to the impairment of these immune responses. Here, we discuss the significance of NKG2D in TNK-mediated anti-tumor activity. Our studies demonstrate that NKG2D+ T cells (TNK) are commonly recruited at the tumor site in melanoma patients where they may exert anti-tumor activity by engaging both TCR and NKG2D. Moreover, NKG2D and TCR triggering was also observed by peripheral blood derived T lymphocyte- or T cell clone-mediated tumor recognition, both in melanoma and colorectal cancer (CRC) patients. Notably, heterogeneous expression of NKG2DLs was found in melanoma and CRC cells, with a decrease of these molecules along with tumor progression. Therefore, through the mechanisms that govern NKG2D engagement in anti-tumor activity and the expression of NKG2DLs by tumor cells that still need to be dissected, we showed that NKG2D expressing TNK cells are a relevant T cell subtype for immunosurveillance of tumors and we propose that new immunotherapeutic interventions for cancer patients should be aimed also at enhancing NKG2DLs expression by tumor cells. [ABSTRACT FROM AUTHOR]

The present paper shows, for the first time, the membrane expression of the dendritic cell maturation marker CD83 on tumor cells from lung cancer patients. CD83 was also detected on freshly cultured fibroblast-like cells from these tissues and on several adherent human tumor cell lines (lung adenocarcinomas P9, A459 and A549, melanomas A375 and C81-61, breast adenocarcinomas SKBR-3 and MCF-7 and colon carcinoma AR42-J), but not in the non-adherent MOT leukemia cell line. CD83 may have immunosuppressive properties and its expression by cancer cells could have a role in facilitating tumor growth. [ABSTRACT FROM AUTHOR]

The first analysis of our clinical trial on interest of using tumor-infiltrating lymphocytes (TIL) as adjuvant therapy for stage III (regional lymph nodes) melanoma was published in 2002 []. The aim of this paper is to update clinical results of 7 years of follow-up after the last treated patient. In the trial conducted between December 1993 and January 1999, patients without any detectable metastases after lymph node excision were randomly assigned to receive either TIL plus interleukin-2 (IL-2) for 2 months, or IL-2 only. The duration of the relapse-free interval was the primary objective. Eighty-eight patients were enrolled in the study. Currently, the last analysis performed in June 2006, after a median follow-up of 114.8 months, did not show change of non-significant extension of the relapse-free interval or overall survival. However, this second analysis strengthens our first hypothesis about the relationship between number of invaded lymph nodes and TIL treatment effectiveness. In the group with only one invaded lymph node, the estimated relapse rate was significantly lower ( P adjusted = 0.0219) and the overall survival was increased ( P adjusted = 0.0125) in the TIL+IL-2 arm compared with the IL-2 only arm. No differences between the two arms, either with regard to the duration of disease-free survival ( P adjusted = 0.38) or overall survival ( P adjusted = 0.43), were noted in the group with more than one invaded lymph node, whatever the number of invaded lymph nodes. Treatment was compatible with normal daily activity. This study, with a very long follow up (median of almost 10 years), postulates for the first time relationship between TIL efficiency in stage III melanoma (AJCC) and number of invaded lymph nodes, indicating that tumor burden might be a crucial factor in the production of an effective in vitro expansion of T cells specific for autologous tumor antigen, a finding which could be of value in future vaccine development for the treatment of melanoma. [ABSTRACT FROM AUTHOR]

The coexistence of tumor progression with a tumor-specific immune response constitutes a major paradox of tumor immunity. During the last decade, the presence of cytotoxic T lymphocytes (CTLs) recognising melanoma-associated antigens has been unequivocally demonstrated in numerous different in vivo and in vitro models. However, most often these melanoma-specific T lymphocytes do not control tumor growth. Several mechanisms that involve changes in melanoma phenotype and/or in T-cell differentiation and function could explain the inability of the immune response to control melanoma. In the last few years it has been demonstrated that cellular cytotoxicity is the result of a balance between activating signals triggered by the TCR and costimulatory molecules and inhibitory signals triggered by inhibitory receptors expressed by the CTL. Because the final outcome of the immune response against melanoma depends on the balance between activating and inhibitory signals, the expression de novo on melanoma cells of ligands for inhibitory NKRs and the down-regulation of costimulatory molecules may favor the escape of tumor cells from immunosurveillance. In this paper we review how altered expression of molecules required for T-cell costimulation could result in impaired lysis of melanoma. The modulation of antimelanoma T-cell responses by a group of receptors originally described on NK cells (NK-associated receptors) but which are now known also to be expressed on a subset of cytolytic effector cells is reviewed. We hypothesize that the expression of ligands for NKRs on melanoma cells may contribute to T-cell–mediated immune responses against melanoma either enhancing or inhibiting activation and differentiation to effector cells. Blocking inhibitory receptors or increasing activating receptors could result in new strategies to improve T-cell–mediated rejection of melanoma. [ABSTRACT FROM AUTHOR]