Reflections on the Histopathology of Tumor-Infiltrating Lymphocytes in Melanoma and the Host Immune Response

Abstract

In the last five decades the role for lymphocytes in host immune response to tumors has been shown, at least in some patients, to be a critical component in disease prognosis. Also, the heterogeneity of lymphocytes has been documented including the existence of regulatory T cells that suppress the immune response. As the functions of lymphocytes have become better defined in terms of antitumor immunity, specific targets on lymphocytes have been uncovered. The appreciation of the role of immune-checkpoints has also led to therapeutic approaches that illustrate the effectiveness of blocking negative regulators of the antitumor immune response. In this Masters of Immunology article, we trace the evolution of our understanding of tumor-infiltrating lymphocytes and discuss their role in melanoma prognosis from the very basic observation of their existence to the latest manipulation of their functions with the result of improvement of the host response against the tumor.

Tumour radiosensitivity is associated with immune activation in solid tumours

“…In contrast, 12-CK was designed using 12 immune-related and inflammation-related genes with the purpose of detecting intra-tumoral lymphoid cell aggregates as a marker of immune activation. (17,19) Twelve CK was previously found to be associated with the presence of TL-ELNs and was able to predict patient outcomes among patients with both colorectal cancer(17) and metastatic melanoma. (18,19) By combining the two gene signatures, we provide evidence for the presence of a clinical interplay between radiosensitivity and immune activation across a wide-variety of tumor types that has not previously been shown in the clinical setting.…”

“…(17) The 12-CK GES has been shown to be associated with the presence of tumor localized ectopic lymph node like structures (TL-ELNs) in both colorectal cancer and metastatic melanoma patients and was associated with improved survival outcomes in both patient populations. (17–19)…”

PD-1 and PD-L1 blockade in gastrointestinal malignancies

“…In patients with CRC, immune infiltrates are a better predictor of survival than TNM classification [8], and patients with MSI colorectal CRC show increased TILs within the tumour micro-environment [50,53]. Antigen-specific TILS that infiltrate the tumour show prognostic and therapeutic significance [54].…”

Metastatic melanoma with features of blue nevus and tumoral melanosis identified during pembrolizumab therapy

“…Although melanoma immunotherapy would be expected to alter microscopic findings, these changes have not yet been well characterized. Targeted and immune response–related therapy can be associated with an increase in tumor-infiltrating lymphocytes 10 . Neoplastic melanocytes may have been present in the skin of our patient and only became apparent secondary to melanosis prompted by pembrolizumab therapy.…”