Contrary to the long held belief that chemotherapy is immunosuppressive, emerging evidence indicates that the anticancer activity of cisplatin is not limited to its ability to inhibit mitosis, but that cisplatin also has important immunomodulatory effects. We therefore methodically examined the relevant preclinical literature and identified four main mechanisms of cisplatin-induced antitumor immunomodulation: (1) MHC class I expression upregulation; (2) recruitment and proliferation of effector cells; (3) upregulation of the lytic activity of cytotoxic effectors; and (4) downregulation of the immunosuppressive microenvironment. Cisplatin-based combination chemotherapy’s antitumor immunomodulatory effects are also beginning to be harnessed in the clinic; we therefore additionally reviewed the applicable clinical literature and discussed how monitoring various components of the immune system (and their responses to cisplatin) can add new levels of sophistication to disease monitoring and prognostication. In summation, this growing body of literature on cisplatin-induced antitumor immunomodulation ultimately highlights the therapeutic potential of synergistic strategies that combine traditional chemotherapy with immunotherapy.

Introduction Resuscitation of rapidly bleeding trauma patients with units of packed red blood cells (RBCs) and plasma given in a 1:1 ratio has been associated with improved outcome. However, demonstration of a benefit is confounded by survivor bias, and past work from our group has been unable to demonstrate a benefit. Methods We identified 438 adult direct primary trauma admissions at risk for massive transfusion who got ≥5 RBC units in the first 24 hours and had a probability of survival of 0.010 to 0.975. We correlated survival with RBC and plasma use by hour, both as a ratio (units of plasma/units of RBC) and a plasma deficit (units of RBC – units of plasma) in the group as a whole and among those using 5–9 and >9 units of RBC. Results Resuscitation was essentially complete in 58.3% by the end of the third hour and 77.9% by the end of the 6th hour. Mortality by hour was significantly associated with worse plasma deficit status in the first 2 hours of resuscitation (P<0.001 and 0.01) but not with plasma ratio. In a subgroup with TRISS 0.200–0.800, early plasma repletion was associated with less blood product use independently of injury severity (P<0.001). Conclusions 1) The efficacy of plasma repletion plays out in the first few hours of resuscitation; 2) plasma deficit may be a more sensitive marker of efficacy in some populations; and 3) early plasma repletion appears to prevent some patients from going on to require massive transfusion.

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High FFP:RBC ratio confers survival benefits in trauma and non-trauma settings, with the highest survival benefit at 1:1.5.