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In CRC, combining 5FU with DNA-damaging agents oxaliplatin and/or irinotecan was an empirical choice rather than a rationally designed strategy, and no new combination partners have been added since the introduction of the biological EGFR and VEGF-targeting agents in the early 2000s

It can be hypothesized that tissue-resident memory T cells are recruited to the skin via the CXCR3 chemokine axis, encounter IL-15 presented in trans by keratinocyte-forming cells, upregulate IFN- at the dermal-epidermal junction, and subsequently induce the death of MCs through the perforin-granzyme pathway (Fig