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We show that these models represented both ‘hot’ and ‘cold’ tumors with high and low levels of intratumoral infiltrates, respectively.

To this end, we characterized several commonly used xenograft models across a range of tumor types in CD34 + humanized non-obese diabetic-scid gamma (NSG) mice. 7–10 Whereas checkpoint modulators have shown antitumor activity in humanized mice, there are limited data reporting characterization on human immune cell subsets within these tumors. 3 6 Despite this, the use of antibodies against PD-1 has shown efficacy in human xenograft and patient-derived xenograft tumors in these mice, demonstrating that these cells can generate antitumor responses. In this model, lymphocytes and dendritic cells have been shown to be at least partially functional however, in general, lesser functionality has been observed for natural killer (NK), B and myeloid cells in CD34 + humanized mice. 3–5 One type of humanized mouse is generated through the use of CD34 + stem cells from cord blood donors. Significant advancement in the development of humanized mouse models has been made. Therefore, there is a need for well-characterized humanized tumor models to inform rational model selection.

However, many times, the therapeutic agent under evaluation only recognizes human isoforms or the expression level of targets of interest are different between human and mouse immune cell subsets. For many therapeutic targets, the use of syngeneic models can be appropriate, assuming that the therapeutic agent functionally modulates mouse isoforms of the target. The use of in vivo preclinical models is critical for establishing activity of drug candidates prior to entering the clinic. 1 2 However, many patients do not respond to checkpoint blockade, and additional therapies are needed to treat these patients. Activation of the immune system via checkpoint blockade, through the use of antibodies against programmed death receptor 1 (PD-1) and programmed death ligand 1 (PD-L1), and cytotoxic T-lymphocyte-associated protein 4, has been shown to produce antitumor responses in patients with a range of cancer types.

Immunotherapy is a promising therapeutic intervention for cancer treatment.