7:21 PM
Mar 28, 2019
 |  BC Innovations  |  Targets & Mechanisms

AACR moves in a myeloid direction

A survey of the hot topics covered in this year’s AACR abstracts

Myeloid cells are showing up everywhere at this year’s AACR conference, suggesting the research community is rapidly expanding the ways it can harness the cell types to improve cancer immunotherapy responses.

One of those ways is by manipulating the microbiome -- another standout topic among this year’s abstracts -- to take advantage of the microbiome’s impact on immune cell populations in the tumor microenvironment.

In its fourth annual analysis, BioCentury surveyed the 5,030 abstracts published in advance of the American Association for Cancer Research (AACR) meeting, which will take place March 29-April 3 in Atlanta.

The survey identifies 25 new and 45 emerging targets and documents a shift towards myeloid cells, where researchers are finding ways to either block these immunosuppressive cells or convert them to active agents that could boost the potency of the first generation of T cell based therapies.

The momentum is now on strategies to convert the immunosuppressive tumor microenvironment to an immunostimulatory one.

The trend suggests the research community is moving forward from a major theme that has run through the conference, and the industry, over the past few years, which is to design cell therapies, such as CAR Ts, to kill cancer cells.

The momentum is now on strategies to convert the immunosuppressive tumor microenvironment to an immunostimulatory one.

This year’s abstracts also show progress in deploying the microbiome to manipulate antitumor immunity. Instead of focusing largely on gut microbiome-derived prognostic markers, as has been the case in previous years, the new studies focus on therapeutic interventions targeting the body’s various microbiomes, including the microbial community inside the tumors themselves.

Other abstracts show a rising interest in nanoparticle-based formulations of cancer therapies, reflecting the expansion of new modalities such as nucleic acid-based therapies and oncolytic viruses that depend on such delivery mechanisms.

The survey also points to a few emerging areas to watch in cancer, including targeted protein degradation and chromatin remodeling, and finds a slight dip in breast cancer’s dominance over other indications.

Myeloid in focus

An interest in myeloid cells is apparent across BioCentury’s analyses. The surge in abstracts discussing myeloid cell subsets suggests the research community is drilling down to the targets that might improve immunotherapy responses.

Myeloid cells are particularly interesting tumor microenvironment targets because they exist in both immunosuppressive and immunostimulatory forms, often classed as M2 and M1 macrophages, respectively. Converting from the former to the latter takes the brakes off the immune system and steps on the gas at the same time (see “Flipping the Switch in Immuno-oncology”).

The number of abstracts covering T cell therapies declined from last year’s meeting, while interest in complementary strategies that make existing cell therapies work better is on the rise.

Specifically, more abstracts mention Tregs, dendritic cells and NK cells this year, while fewer discuss CAR Ts and engineered TCR cells (see Figure: “AACR 2019 cell types”).

Figure: AACR 2019 cell types

Using cell type mentions in abstracts at AACR 2019 as a readout for where cancer research is focused shows tumor-associated macrophages still dominating the field, although slightly less so than last year. The American Association for Cancer Research (AACR) 2019 annual meeting produced a similar pattern to the 2018 meeting, with some areas, like CAR T cells, showing an arguably surprising drop, given the pace of product development in the field. Among the newer cell type mentions there was more variability. Mentions of engineered TCR cells fell by half, from 19 to 9, but neoantigen-specific T cells jumped to 14 mentions from just 1 in 2018. Abstracts were searched for mentions of the selected cell types shown, and include mentions of the cells either as therapeutic agents or in the context of therapies that inhibit, activate or recruit the cells. CD4+ cells, CD8+ cells, and other cells were excluded from the search as they were frequently mentioned in abstracts where they were neither a therapeutic agent nor the targeted cell type. Source: AACR abstracts as of Feb. 27

Although the general class of tumor-associated macrophages -- which can either suppress or promote tumor formation -- is down this year by about 100, the total number of abstracts is also down, falling by 554 from 2018.

Drilling into individual myeloid cell types shows myeloid-derived suppressor cells (MDSCs) feature in 96 of this year’s abstracts, up 12% from last year’s count of 86, and 14% more mention M1 or M2 macrophages this year (105) than last (92).

Those abstracts represent a mix of strategies, including depleting immunosuppressive MDSCs or M2 macrophages, and converting M2 macrophages to the immunostimulatory M1 phenotype (see Figure: “Turning up the heat with myeloid cells”).

Figure: Turning up the heat with myeloid cells

The race is on to turn cold tumors hot, making them more responsive to the growing collection of checkpoint inhibitors and other immunotherapies nearing the market. At the 2019 American Association for Cancer Research (AACR) meeting, targeting myeloid cell subpopulations to that end is one of the major themes running through the abstracts.

Although heterogeneity among myeloid cell populations...

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