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. 2021 Jan 25;13(3):440. doi: 10.3390/cancers13030440

Table 1.

Advantages and drawbacks of different preclinical models of PDAC for immunobiology studies.

Model Principle Benefits Caveats
Syngeneic Pan02 cell line Established mouse tumor cell lines transplanted (subcutaneous or orthotopic) into immune-competent C57BL/6J mice

  1. Presence of an intact immune system

  2. Tumor microenvironment is strongly immunosuppressive and scarce in effector CD8+ T-cells

  3. Tumors are intrinsically resistant to a wide range of chemotherapeutics

  4. Subcutaneously implanted tumors can be easily monitored and measured

  1. Limited desmoplastic reaction

  2. High mutational load since derived from a carcinogen-induced tumor

  3. Lack Kras mutation

  4. Higher response to anti-PD-1 and anti-CTLA-4 antibodies than what is typically seen in human tumors
Syngeneic KPC-derived cell lines Established mouse tumor cell lines transplanted (subcutaneous or orthotopic) into immune-competent C57BL/6J mice

  1. Presence of an intact immune system

  2. Tumor microenvironment is strongly immunosuppressive

  3. Tumors display desmoplastic reaction

  4. Tumors demonstrate low incidence of missense mutations and lack of neoepitopes, similar to human tumors

  5. Subcutaneously implanted tumors can be easily monitored and measured

  1. Tumors exhibit variable abundance of intratumoral CD8+ T-cells

  2. Tumors do not fully mimic the sequential accumulation of mutations seen in human cancers

  3. Tumors derived from late passages have unpredictable and unexpected alterations in the microenvironment

  4. The tumor microenvironment of subcutaneous tumor may not be reflective that of orthotopic tumors
Genetically-engineered KPC mouse model Concurrent activation of KrasG12D and loss of p53 in the pancreas to allow for spontaneous tumor development

  1. Presence of an intact immune system

  2. Tumor microenvironment is strongly immunosuppressive

  3. Histopathological features closely resemble human tumors: cellular morphology, poor vascularity, pronounced desmoplasia, and metastatic spread

  4. Tumors demonstrate low incidence of missense mutations and lack of neoepitopes

  1. Tumors exhibit variable abundance of intratumoral CD8+ T-cells

  2. Tumors can have higher abundance of myeloid cells than what is seen in human tumors

  3. Low throughput and high investment
Patient-Derived Xenograft (PDX) Mouse Models Human PDAC tumors implanted in immune-deficient host

  1. Early passaged PDX tumors preserve the tumor histology and the genetic heterogeneity of host patients

  2. PDX tumors show consistent biological properties and stable phenotypes across multiple passages

  3. PDX tumors show therapeutic responses similar to what seen in patients

  1. Tumor-bearing mice lack an intact immune system

  2. Surgical implantation is required with low engraftment rates

  3. PDX tumors do not faithfully represent the stroma of the original PDAC tumor

  4. Heterogeneity may be lost in subsequent serial passages

  5. Propagation and expansion of orthotopic tumors can be challenging
Organoid cultures Tumor cells isolated from human tumors allowed to grow into 3D structures in specialized growth media

  1. PDAC organoids maintain tumor heterogeneity and mutational complexity after serial passages

  2. PDAC organoids retain the extensive stromal reaction when orthotopically implanted in mice

  3. PDAC organoids can be from both resected tumor specimens and metastatic disease with high engraftment rates

  4. PDAC organoids show chemotherapeutic responses similar to what seen in patients

  1. Establishment and maintenance of organoids is labor- and time-intensive

  2. PDAC organoids grown in culture often lack a tumor microenvironment, including fibroblasts and immune cells
Ex vivo slice cultures 250 µm to 400 µm thick sections from human PDAC tumors maintained and cultured in vitro

  1. Slice cultures maintain tumor morphology, proliferation, and viability ex vivo

  2. The original integrity of the PDAC tumor microenvironment is maintained, with stromal cells surviving culture conditions

  3. Slice cultures retain immune infiltrates from the host patients

  1. Current slice culture conditions do not allow for long-term treatment (only up to 1 week)

  2. Significant heterogeneity in the distribution of immune cells are seen with slices dissected from different regions

  3. Current slice cultures do not allow for evaluation of primed immune cells entering the tumor from the circulation