Publications

Skin dendritic cells in melanoma are key for successful checkpoint blockade therapy

Prokopi et al. JITC (2021)
Immune profiling in the tumor and tumor-draining lymph nodes during progression and treatment reveals distinct changes in DC and T cell subset frequencies, migration, and recruitment
Immune profiling in the tumor and tumor-draining lymph nodes during progression and treatment reveals distinct changes in DC and T cell subset frequencies, migration, and recruitment

Checkpoint blockade helps T cells recognize and attack cancer cells by inhibiting the “off” immune signals, but it is not effective for all melanoma patients. Through a multi-institution collaboration, Prokopi A, Tripp CH, Tummers B, et al. set out to understand the underlying mechanisms and crucial role of dermal dendritic cells (DCs) in a melanoma mouse model. 

Migrating conventional DC1 (cDC1) and cDC2 are two major dermal subsets presenting tumor antigens to cytotoxic T cells. Using a previously-published 37-marker mass cytometry panel incorporating surface marker and transcription factors differentially expressed in six unique DC subsets [1], the researchers observed a gradual loss of the dermal cDC2 with melanoma progression, whereas the cDC1 numbers remained unchanged. Furthermore, they found that boosting DC activation using Flt3L, in combination with polyI:C and anti-CD40 could increase both cDC1 and cDC2 numbers within the tumor and increased migration of cDC2 cells to tumor-draining lymph nodes. Furthermore, it was discovered that boosted cDCs efficiently deliver gp100 tumor-associated antigen to gp100-specific CD8+ T cells. As a result, combining the DC boost with checkpoint blockade antibodies against PD-1 and TIM-3 slowed melanoma growth and extended survival in mice.

This study indicated that responsiveness to checkpoint blockade may benefit from boosting the numbers and function of DCs. It also demonstrated the value of high-dimensional mass cytometry in identifying immune subsets that equip  T cell-based immunotherapies with effective anti-tumor cytotoxicity.

Reference citation: Prokopi A, Tripp CH, Tummers B, et al. Skin dendritic cells in melanoma are key for successful checkpoint blockade therapy. Journal for ImmunoTherapy of Cancer. 2021. 9:e000832. doi: 10.1136/jitc-2020-000832

Additional References:

[1] Guilliams M, Dutertre CA, Scott CL, McGovern N, Sichien D, et al. Unsupervised High-Dimensional Analysis Aligns Dendritic Cells across Tissues and Species. Immunity. 2016 Sep 20;45(3):669-684. doi: 10.1016/j.immuni.2016.08.015. Epub 2016 Sep 13.

You Might Also Like

Illustration. In the center is a grey mass labeled "tumor" under a magnifying glass. Inside the tumor are three grey cells all with "zzz" above them. Outside the magnifying glass (and therefore outside the tumor) in the four corners are different depictions. Top left shows three red cells and is labeled "novel T cell clones". Top right shows a lymph node with red T cell zones and the words "LN trafficking required". Bottom right shows two red T cells in a blood vessel labeled "LAG-3 and CD8+" with the words "peripheral biomarkers". Bottom left shows a spleen with the same grey, sleeping T cells. There's a red lightning bolt and the words "impaired systemic immune response in cancer".

Peripheral blood analysis is key to developing effective cancer immunotherapies

Although most research focuses on tumor-killing immune cells at the site of the tumor, new research increasingly demonstrates the value of studying circulating immune cells in peripheral blood to identify new therapeutic targets to enhance tumor-killing immune responses. We highlight recent publications with peripheral blood biomarkers and discuss recommendations for how to incorporate peripheral blood immune profiling into your drug development pipeline.