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Page 10 of 14 Diab et al. J Cancer Metastasis Treat 2022;8:42 https://dx.doi.org/10.20517/2394-4722.2022.60

Table 1. Clinical trials evaluating therapeutic approaches for PDAC TME
NCT number Target Drug Reference
NCT03336216 CSF1R Cabiralizumab [51]
NCT01413022, NCT02732938 CCR2 PF-04136309 [52,53]
NCT03214250 CD40 Sotigalimab [57]
NCT04191421 PD-1, IL-6 Spartalizumab, siltuximab [67]
NCT02826486 CXCR4 Motixafortide [68]

PDAC: Pancreatic adenocarcinoma; TME: tumor microenvironment.

and their presence is associated with poor prognosis [101,102] . They reside within the tumor and suppress the
anti-tumoral activities of αβ T cells [101,102] . Lastly, the innate lymphoid cells (ILCs) groups 1, 2, and 3
[103]
represent a heterogeneous group of tissue-resident cells that play conflicting roles in solids tumors . In
PDAC, ILC2s were shown to amplify PD-1 blockade by activating tissue-specific cancer immunity through
IL-33-dependent mechanisms . Targeting these subsets for the treatment of PDAC is still in its infancy.
[104]
Table 1 summarizes the efforts aimed at targeting the immune populations of the TME.

CONCLUSION
Previously regarded as an “immune desert”, we now know that the TME of PDAC is enriched with immune
cells that play both pro- and anti-tumoral roles and interact very intimately with tumor cells as well as the
other cellular populations in the TME. Many of the pro-tumoral immune subsets are present in the very
early stages of cancer development and govern the progression and metastases of PDAC through
mechanisms that include producing a dense stroma, creating a niche in metastatic sites, and maintaining an
immune suppressive environment that inhibits the activities of anti-tumoral populations. However, recent
advances in single-cell analysis highlight several anti-tumoral subsets that are not only associated with
improved survival but can also be used as therapeutic targets. Ongoing trials are studying novel dendritic
cell vaccines, as well as different combinations of immune modulators with immune checkpoint inhibitors
in an attempt to render “cold” tumors into “hot” tumors. Additionally, more research is urgently needed to
better identify the potential role of rarer subsets, such as NK cells, as therapeutic targets.

DECLARATIONS
Authors’ contributions
Contributed significantly to the generation of this manuscript: Diab M, El-Rayes BF

Availability of data and materials
Not applicable.

Financial support and sponsorship
None.

Conflicts of interest
Both authors declared that there are no conflicts of interest.

Ethical approval and consent to participate
Not applicable.