Networks of CD8+ T Cell Response Activation in Melanoma and Vitiligo

Abstract

Melanoma is an aggressive skin cancer derived from melanocyte, which shows high response rate to cancer immunotherapy, such as immune checkpoint inhibitors (ICIs). Vitiligo is an autoimmune skin disease resulting from the destruction of melanocytes by autoreactive CD8+ T cells. Vitiligo induced by cancer immunotherapy is a favorable prognostic factor in patients with melanoma, and growing evidence supports the fact that melanocyte/melanoma-shared antigen (MSA)-specific CD8+ T cells infiltrated in the tumor (melanoma) and skin (vitiligo) microenvironment play pivotal roles in the prognosis of both diseases. Thus, cellular communications that promote MSA-specific CD8+ T cells recruitment, proliferation, and effector functions are now seen as key targets to enhance the efficacy of current therapies for both diseases. Here, we discussed recent advancements in illustrating immune signaling pathways and immune cell types that regulate migration, proliferation, and function of MSA-specific CD8+ T cells in melanoma and vitiligo; and future immunotherapeutic approaches that may enhance clinical outcomes of both diseases.

Does immune dysregulation contribute towards development of hypopigmentation in Indian post kala‐azar dermal leishmaniasis?

“…increased presence of CD8 + T-cells and TNFα, both in circulation and skin) that contribute towards the disease pathogenesis. [36][37][38][39] The collection of skin biopsies from healthy individuals is challenging; accordingly as our study was based on the immunohistochemical analysis of melanocytespecific markers in the skin, the foreskin of males undergoing voluntary circumcision was included, as also skin sections from laboratory volunteers. Importantly, the staining pattern from both sources was comparable and corroborated with a study by Michalak-Micka et al 40 involving the characterization of the melanocyte progenitor population in human interfollicular epidermis, where expression of melanocyte-specific markers was comparable between human foreskin and other anatomical skin sites.…”

Immunotherapy for Melanoma: The Significance of Immune Checkpoint Inhibitors for the Treatment of Advanced Melanoma

“…Since these cutaneous irAEs described above suggest enhancement of the immune responses in tumor-bearing hosts, the onset of irAEs might correlate with the efficacy of ICIs for the treatment of advanced melanoma [ 53 , 62 , 63 ]. Indeed, the appearance of any cutaneous irAEs was significantly protective against mortality (hazard ratio (HR): 0.778; 95% CI 0.725–0.834; p < 0.001) [ 53 ].…”

“…Indeed, the appearance of any cutaneous irAEs was significantly protective against mortality (hazard ratio (HR): 0.778; 95% CI 0.725–0.834; p < 0.001) [ 53 ]. Moreover, several reports focused on vitiligo as a cutaneous irAE that was correlated with a good prognosis of advanced melanoma treated with anti-PD1 Abs [ 62 , 63 ]. For example, vitiligo induced by anti-PD1 Abs is a factor associated with a good prognosis in patients with melanoma, and melanocyte/melanoma-shared antigen (MSA)-specific CD8+ T cells play significant roles in the prognosis of melanoma [ 62 ].…”

“…Moreover, several reports focused on vitiligo as a cutaneous irAE that was correlated with a good prognosis of advanced melanoma treated with anti-PD1 Abs [ 62 , 63 ]. For example, vitiligo induced by anti-PD1 Abs is a factor associated with a good prognosis in patients with melanoma, and melanocyte/melanoma-shared antigen (MSA)-specific CD8+ T cells play significant roles in the prognosis of melanoma [ 62 ]. In another report, both the onset of vitiligo and an increased serum CCL19 level were correlated with a better prognosis in advanced melanoma patients treated with anti-PD1 Abs [ 63 ].…”

A CD8+ T cell-associated immune gene panel for prediction of the prognosis and immunotherapeutic effect of melanoma

“…In particular, on the condition of the approval of the use of CTLA-4 , PD-L1 , and PD-1 -specific immune checkpoint inhibitors, immunotherapy performs better than conventional therapies in lengthening the overall survival (OS) of cases of heterogeneous tumors ( 6 – 9 ). SKCM is a class of tumor displaying the most sensitive to immunotherapeutic methods ( 10 , 11 ). According to the latest clinical study, after SKCM patients underwent nivolumab + ipilimumab combination therapy, the 5-year OS rate was 52% ( 12 ).…”