Tissue-resident memory CD8+ T cells promote melanoma–immune equilibrium in skin

Park, Simone L.; Buzzai, Anthony; Rautela, Jai; Hor, Jyh Liang; Hochheiser, Katharina; Effern, Maike; McBain, Nathan; Wagner, Teagan; Edwards, Jarem; McConville, Robyn; Wilmott, James S.; Scolyer, Richard A.; Tüting, Thomas; Palendira, Umaimainthan; Gyorki, David E.; Mueller, Scott N.; Huntington, Nicholas D.; Bedoui, Sammy; Hölzel, Michael; Mackay, Laura K.; Waithman, Jason; Gebhardt, Thomas

doi:10.1038/s41586-018-0812-9

Cited by 290 publications

(244 citation statements)

References 32 publications

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“…This is in line with recent reports demonstrating the presence of CD103 + T RM in close proximity to tumor cells in patients with different types of cancers, including melanoma and breast cancer . Such results further echo our findings in mouse skin where T RM cells can directly interact with and control dormant melanoma microlesions . Furthermore, clustering of antigen‐specific T RM cells with infected cells has been observed in the context of genital Herpes simplex virus (HSV)‐2 infection in human genital skin and in response to HSV‐1‐infection in mouse skin, suggesting that accumulation of T RM cells preferentially occurs in the context of abnormal or infected but not normal cells .…”

Section: Discussionsupporting

confidence: 92%

“…In line with this, recent reports have shown that T RM cells afford potent antitumor immunity in mouse models . Furthermore, we have recently demonstrated that T RM cells can promote cancer‐immune equilibrium in mouse skin by keeping dispersed melanoma cells dormant over extended periods of time . Whether T RM cells have a similar function in maintaining tumor dormancy in humans, however, remains to be addressed.…”

Section: Introductionsupporting

confidence: 56%

“…A number of recent preclinical studies have revealed an important role for T RM cells in melanoma surveillance. In line with this, we have recently shown that CD8 + CD103 + T RM cells promote cancer‐immune equilibrium and thereby prevent the outgrowth of residual melanoma cells that can persist in mouse skin over extended periods of time . Accordingly, the generation of large numbers of T RM cells in skin is associated with improved immune control and suppressed cancer progression.…”

Section: Discussionmentioning

confidence: 61%

“…T RM cells were comparatively sparse in the overt ITM and were, together with other T‐cell subsets, largely excluded from the centre and restricted to the tumor margin. This again reflects a cohort of escaped tumors in preclinical models, where T RM cells are mainly found at the margin but not in the centre of progressing tumors …”

Section: Discussionmentioning

confidence: 82%

“…However, the natural history of the occult metastasis is unpredictable. It may represent the first step in escape from immune equilibrium, or, as seen in mouse models, it may also reflect temporary tumor growth before return to immune control and quiescence, which could have lasted for a prolonged period of time if not indefinitely. Lastly, although tumor‐associated CD103 + T RM ‐like cells are often enriched for cancer‐specific cells, a large fraction of these may be made up of virus‐specific T RM cells that were generated during previous infections .…”

Section: Discussionmentioning

confidence: 99%

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Accumulation of CD103⁺ CD8⁺ T cells in a cutaneous melanoma micrometastasis

et al. 2019

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Objective The immune system can halt cancer progression by suppressing outgrowth of clinically occult micrometastases in a state of cancer‐immune equilibrium. Cutaneous melanoma provides a unique opportunity to study the immune contexture of such lesions, as miniscule skin metastases are accessible to clinical inspection and diagnostic biopsy. Methods Here, we analysed by multiplex immunofluorescence microscopy samples from a melanoma patient presenting with an overt and an occult in‐transit metastasis (ITM), the latter of which appeared as a small erythematous papule. Results Microarchitecture and immune composition in the two lesions were vastly different. CD4+ and CD8+ T cells accumulated around the margin of the overt SOX10+ Melan A+ ITM but were largely excluded from the tumor centre. By contrast, the occult micrometastasis contained only few SOX10+ Melan A− melanoma cells which were scattered within a dense infiltrate of T cells, including a prominent population of CD103+ CD8+ T cells resembling tissue‐resident memory T (TRM) cells. Notably, almost every single melanoma cell in the micrometastasis was in close proximity to these TRM‐like cells. Conclusion Such results support the emerging concept that CD103+ CD8+ TRM cells are key mediators of cancer surveillance and imply an important function of these cells in controlling clinically occult micrometastases in humans.

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Section: Discussionsupporting

confidence: 92%

Section: Introductionsupporting

confidence: 56%

Section: Discussionmentioning

confidence: 61%

Section: Discussionmentioning

confidence: 82%

Section: Discussionmentioning

confidence: 99%

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Accumulation of CD103⁺ CD8⁺ T cells in a cutaneous melanoma micrometastasis

et al. 2019

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Non‐Invasive Transdermal Delivery Systems with Deep Tissue Penetrating Ability for Local ROS‐Modulating Chemotherapy

Deng

Zhuang

Ying

et al. 2022

Adv Funct Materials

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Cutaneous melanoma is the deadliest malignant skin cancer due to its poor prognosis, rapid local growth, and high metastasis. Transdermal administration for local drug delivery would be one of the most appropriate therapy regimens. However, promoting drug penetration into deep tumor tissue and maintaining the balance of redox homeostasis during the antitumor treatment to inhibit melanoma progression remains a great challenge in melanoma treatment. Herein, non‐invasive transdermal delivery systems are reported for melanoma treatment, which is composed of biocompatible hydrogel and penetrating nanocarriers. Highly penetrating nanocarriers can co‐deliver paclitaxel and coenzyme Q10 for inhibiting melanoma and reducing side effects, which are attributed to drug encapsulation, deep tissue penetration, high cellular uptake, and organelle targeting. More importantly, biocompatible hydrogels serve as nanocarriers platforms for melanoma location and transdermal delivery. This hierarchical nanoparticle‐hydrogel system achieves high‐efficiency non‐invasive transdermal delivery for inhibiting melanoma, blocking adverse effects, and restraining melanoma development.

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Exploiting Unique Features of Microneedles to Modulate Immunity

et al. 2023

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Microneedle arrays (MNAs) are small patches containing hundreds of short projections that deliver signals directly to dermal layers without causing pain. These technologies are of special interest for immunotherapy and vaccine delivery because they directly target immune cells concentrated in the skin. The targeting abilities of MNAs result in efficient immune responses—often more protective or therapeutic—compared to conventional needle delivery. MNAs also offer logistical benefits, such as self‐administration and transportation without refrigeration. Thus, numerous preclinical and clinical studies are exploring these technologies. Here we discuss the unique advantages of MNA, as well as critical challenges – such as manufacturing and sterility issues – the field faces to enable widespread deployment. We explain how MNA design parameters can be exploited for controlled release of vaccines and immunotherapies, and the application to preclinical models of infection, cancer, autoimmunity, and allergies. We also discuss specific strategies to reduce off‐target effects compared to conventional vaccine delivery routes, and novel chemical and manufacturing controls that enable cargo stability in MNAs across flexible intervals and temperatures. We then examine clinical research using MNAs. We conclude with drawbacks of MNAs and the implications, and emerging opportunities to exploit MNAs for immune engineering and clinical use.This article is protected by copyright. All rights reserved

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Tissue-resident memory CD8+ T cells promote melanoma–immune equilibrium in skin

Cited by 290 publications

References 32 publications

Accumulation of CD103⁺ CD8⁺ T cells in a cutaneous melanoma micrometastasis

Accumulation of CD103⁺ CD8⁺ T cells in a cutaneous melanoma micrometastasis

Non‐Invasive Transdermal Delivery Systems with Deep Tissue Penetrating Ability for Local ROS‐Modulating Chemotherapy

Exploiting Unique Features of Microneedles to Modulate Immunity

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Tissue-resident memory CD8+ T cells promote melanoma–immune equilibrium in skin

Cited by 290 publications

References 32 publications

Accumulation of CD103+ CD8+ T cells in a cutaneous melanoma micrometastasis

Accumulation of CD103+ CD8+ T cells in a cutaneous melanoma micrometastasis

Non‐Invasive Transdermal Delivery Systems with Deep Tissue Penetrating Ability for Local ROS‐Modulating Chemotherapy

Exploiting Unique Features of Microneedles to Modulate Immunity

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Product

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Accumulation of CD103⁺ CD8⁺ T cells in a cutaneous melanoma micrometastasis

Accumulation of CD103⁺ CD8⁺ T cells in a cutaneous melanoma micrometastasis