Chemotherapy

research highlights chemotherapy conventional chemotherapy boosts the effect of cancer vaccines therapeutic cancer vaccines have been immunotherapy (cancer vaccine and developed as an alternative treatment adoptive t-cell therapy), and three option to conventional chemotherapy different drugs (paclitaxel, cisplatin, and radiotherapy. However, evidence has and doxorubicin) in several different indicated that therapeutic cancer vaccines tumor models in vivo and in vitro in given as a single agent may not produce mouse cells and in vitro in human cells. substantial clinical benefits. recent each of the drugs used have different data suggest that the benefit of cancer mechanisms of action: paclitaxel induces immunotherapies can be improved when apoptosis by interfering with the normal combined with conventional methods function of microtubule breakdown; of treatment. to date, however, the cisplatin induces apoptosis by binding mechanisms involved in this occurrence to and causing crosslinking of Dna; have remained unknown. doxorubicin interferes with Dna and now, a mechanism by which cancer prevents replication. immunotherapies mediate a potent all three chemotherapeutic drugs antitumor effect when combined with sensitized the tumor cells, making them conventional chemotherapeutics has more susceptible to attack from Ctls. of been uncovered in mice by a team of note, the researchers observed that in the researchers led by Dmitry Gabrilovich absence of chemotherapy, the Ctls were at the H. lee moffitt Cancer Center and only able to target tumor cells expressing research institute, tampa, usa. “we specific antigens. By contrast, following of mannose–6–phosphate receptor on have found that chemotherapy synergized chemotherapy, the Ctls were also tumor cells induced by chemotherapy”. with immunotherapy in the killing of able to exert their cytotoxic effects on thus, nonspecific toxic effects associated tumor cells,” says Gabrilovich. tumor cells that did not express specific with conventional chemotherapy the aim of cancer immunotherapy antigens. “this effect was mediated by should not be increased as the enhanced is to induce an immune response increased penetration of granzyme B antitumor effect of combined treatment is through the production of cytotoxic released by Ctls into tumor cells in limited to those cells that are sensitive to t lymphocytes (Ctls) that target specific [a] perforin-independent manner,” chemotherapeutic agents. tumor antigens and kill tumor cells. Gabrilovich comments. this study has uncovered a potentially Chemotherapy is usually associated Granzyme B is a critical mediator of novel therapeutic approach for the with immunosuppressive effects; thus, cell apoptosis by Ctls in cell-mediated treatment of advanced-stage cancer. “the conventional chemotherapy was not immune response. the chemotherapeutic main implication for future research is previously considered as an attractive drugs increased the permeability of tumor that cancer immunotherapy can be tried adjunct to cancer immunotherapy. cell membranes to granzyme B, which can as frontline treatment in combination However, high rates of clinical responses penetrate neighboring tumor cells that do with conventional chemotherapy have been reported in several clinical not express the specific antigen that the in patients with advanced cancers,” trials using various combinations of Ctls target. these cells in turn release describes Gabrilovich. “the overall chemotherapy regimens and cancer granzyme B, which the investigators concept needs to be confirmed in detailed vaccines in patients with a wide range suggest is responsible for increasing studies in patient’s samples, the time of of cancers. “this observation suggested the sensitivity of the cells to Ctls intervention needs to be worked out as that there is a common mechanism generated by cancer immunotherapies. well as the mechanism of mannose–6– underlying this potentially important activated Ctls were, therefore, able phospate up-regulation,” he concludes. phenomenon,” Gabrilovich explains. His to kill neighboring tumor cells without Lisa Richards team, therefore, decided to move from the coming into direct contact with them. bedside back to the bench to identify Gabrilovich suggests that this effect could Original article Ramakrishnan, R. et al. Chemotherapy the mechanism involved. dramatically increase the potency of enhances tumor cell susceptibility to CTL-mediated killing Gabrilovich and colleagues tested the antitumor activity of Ctls, adding during cancer immunotherapy in mice. J. Clin. Invest. 120, the effects of two types of cancer “this effect is mediated via upregulation 1111–1124 (2010)