Specific Aim 3: We will investigate how key components of a tumor and the host contribute to cancer biology 

Reciprocal interactions between accessory cells, their mediators, structural components of the extracellular matrix, and genetically altered neoplastic cells regulate all aspects of tumorigenicity and possible treatment resistance. Thus, JAXCC members investigate tumor and host microenvironments: the cancer cell intrinsic and extrinsic components of a malignant tumor. The vision is to integrate genetic alterations identified in Aim 2 with models developed in Aim 1 and with the unique expertise of JAXCC members involved in the work of Aim 3 to deconvolute these complex interactions. This in turn will enable the identification of novel candidate biomarkers as well as therapeutic targets.

In ongoing and future work, we will:

1. Identify immunological and stromal mechanisms that determine cancer behavior and treatment response; Research toward this goal brings together experts in autoimmunity, aging, cancer immunology, and the microbiome in a multi-factorial analysis of interactions among cancer cells and the tumor microenvironment.
   
   JAXCC members involved in this work include: Jacques Banchereau, Chih-Hao Chang, Jeff Chuang, Dave Harrison, Ed Liu, Julia Oh, Karolina Palucka, Gary Ren, Paul Robson, Derry Roopenian, Dave Serreze, Lenny Shultz, Jen Trowbridge, Duygu Ucar, Derya Unutmaz, Roel Verhaak, George Weinstock.
   
   
2. Identify and validate biomarkers of treatment sensitivity and resistance in in vivo models; Work towards this goal includes discovery of genetic and epigenetic signatures that alter immune cell function, as well as patterns of immune, stromal cell, and microbial distribution in the tumor microenvironment that may be predictive of treatment response.
   
   JAXCC members involved in this work include: Olga Anczukow, Jacques Banchereau, Jeff Chuang, Ching Lau, Ed Liu, Julia Oh, Karolina Palucka, Lenny Shultz, Jen Trowbridge, Roel Verhaak, George Weinstock.
   
   
3. Develop ways to identify systems vulnerabilities towards better treatments and overcoming acquired insensitivity to therapy; All of the research in this aim seeks to uncover the molecular and cellular interactions among the diverse populations that comprise the tumor microenvironment and determine tumor response to therapy. Developing systems biology models of these dynamics is essential for designing the multi-faceted therapeutic strategies that will be needed for durable responses.