Targeting the Programmed Death-1 Pathway in Lymphoid Neoplasms

T cell activation is explained by the two-signal model proposed by Bretscher and Cohn (Fig. 1).[1] The first signal, which triggers T cell receptor (TCR) signaling, occurs when the major histocompatibility complex (MHC) molecule of an antigen-presenting cell (APC) presents a processed antigen to the TCR of a T cell. The second signal, which is an antigen-independent, co-stimulatory or co-inhibitory signal delivered by the APCs, modulates TCR signaling and determines the T cell’s fate. The prototypical molecule of the second signal is CD28, which constitutively expressed in resting naïve T-cells.

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