Homologous recombination-DNA damage response defects increase TMB and neoantigen load, but not effector T cell density and clonal diversity in pancreatic cancer.

HRD-positive PDACs showed a trend towards a higher mutation number (p < 0.0001), CNV burden (p = 0.0004) and SV number (p < 0.0001) per tumor when compared to HRD-negative PDACs.

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Consistently, we observed a significantly lower Shannon Diversity Index and a strong trend (p = 0.0910) for unique CDR3 in PDACs with alterations in BRCA1/BRCA2/PALB2 compared to PDAC without alterations in these genes (p = 0.0291) (Fig. 2 E–F; Table S7).

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Interestingly, even though HRD is associated with an increased neoantigen load, HRD-positive status (p = 0.1878), higher TMB (p = 0.0906), and higher neoantigen load (p = 0.0041; p = 0.0242), were all associated with a decreasing trend of CD8 + T lymphocytes (Fig. 1 G–H; Table S7).

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