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The high grade ofphenotype plasticity of monocytes macrophages, is resumed in two different cell subsets named M1 or M2. Several studies of microbial infections in vitro and in vivo, showed that, during the early stage of infection, macrophages are polarized toward Ml phenotype that should be protective against pathogen, while during the chronic phase of infection/disease macrophages polarize toward M2 phenotype to avoid damages from a prolonged Ml type activation.Obiettivo: In order to investigate if Mycobacterium tuberculosis infection can drive circulating monocytes toward the expression of Ml or M2 phenotypes, we have analyzed by flow cytometry monocytes obtained from patients with active tuberculosis (TB) at early phase of disease and during anti mycobacterial therapy, subjects with latent TB and healthy uninfected control. Risultatil Analysis of surface markers expression showed no clearcut Ml/M2 polarization in all tested groups, but we found a very high percentage of RANK+ monocytes in patients with active TB disease before treatment, while RANK expression was very faint in monocytes from all other experimental groups. Moreover the statistical analysis of geometric MFI of RANK showed a signifìcant difference between patients with active disease compared to all the others groups. Conclusioni: Given that the available in vitro diagnostic tests are limited in discriminating subjects with latent or active disease, as well as response to therapy,,we speculate that the evaluation of RANK expression on monocytes could represent an additional biomarker useful to support diagnosis of active disease and monitor the response to therapy.

Colon cancer comprises a small population of cancer initiating stem cells (CIC) that is responsible for tumor maintenance and resistance to anti-cancer therapies, possibly allowing for tumor recapitulation once treatment stops. Combinations of immune-based therapies with chemotherapy and other anti-tumor agents may be of significant clinical benefit in the treatment of colon cancer. However, cellular immune-based therapies have not been experimented yet in the population of colon CICs. Here, we demonstrate that treatment with low concentrations of commonly used chemotherapeutic agents, 5-fluorouracyl and doxorubicin, sensitize colon CICs to Vγ9Vδ2 T cell cytotoxicity. Vγ9Vδ2 T cell cytotoxicity was largely mediated by TRAIL interaction with DR5, following NKG2D-dependent recognition of colon CIC targets. We conclude that in vivo activation of Vγ9Vδ2 T cells or adoptive administration of ex-vivo expanded Vγ9Vδ2 T cells at suitable intervals after chemotherapy may substantially increase anti-tumor activities and represent a novel strategy for colon cancer immunotherapy.

The broad antimicrobial and antitumoral reactivity of Vgamma9Vdelta2 T cells, their ability to produce inflammatory cytokines involved in protective immunity against intracellular pathogens and tumors and their strong cytolytic and bactericidal activities suggest their direct involvement in immune control of cancers and infections. gammadelta T cells can be selectively activated by naturally occurring or synthetic phosphoantigens, and drugs that enhance their accumulation into stressed cells, offering new avenues for the development of gammadelta T cell-based immunotherapies. The recent development of small drugs selectively activating Vgamma9Vdelta2 T lymphocytes, which upregulate endogenous phosphoantigens, has enabled investigators to design experimental approaches of cancer immunotherapies; several ongoing phase I and II clinical trials are focused on the role of direct bioactivity of drugs and of adoptive cell therapies involving phosphoantigen-activated Vgamma9Vdelta2 T lymphocytes in humans. In this review, we focus on the recent advances of the activation/expansion of gammadelta T cells in vitro and in vivo that may represent a promising target for the design of novel and highly innovative immunotherapy in patients with different types of cancer.