Padhye, A. | bioRxiv Science

bioRxiv2022

A cross taxonomic comparison of bird and butterfly communities of Tamhini Wildlife Sanctuary across two decades.

Human disturbance can alter the structure and function of ecological communities. We studied bird and butterfly communities of Tamhini wildlife sanctuary to understand the effects two decades of changing land use and management. We replicated a previous study conducted between 1998 and 2001, sampling 7 line transects every fortnight between April 2016 and April 2017. We analyzed the diversity and structure of functional groups and compared our findings to previous surveys. Species diversity increased for both taxa, however, community composition was significantly different across studies. Changing land may affect multiple trophic levels and alter community assembly and ecosystem function.

ecology↗

bioRxiv2020

Th17 cells contribute to combination MEK inhibitor and anti-PD-L1 therapy resistance in KRAS/p53 mutant lung cancers

Understanding resistance mechanisms to targeted therapies and immune checkpoint blockade in mutant KRAS lung cancers is critical to developing novel combination therapies and improving patient survival. Here, we show that MEK inhibition enhanced PD-L1 expression while PD-L1 blockade upregulated MAPK signaling in mutant KRAS lung tumors. Combined MEK inhibition with anti-PD-L1 synergistically reduced lung tumor growth and metastasis, but tumors eventually developed resistance to sustained combinatorial therapy. Multi-platform profiling revealed that resistant lung tumors have increased infiltration of Th17 cells, which secrete IL-17 and IL-22 cytokines to promote lung cancer cell invasiveness and MEK inhibitor resistance. Antibody depletion of IL-17A in combination with MEK inhibition and PD-L1 blockade markedly reduced therapy-resistance in vivo. Clinically, increased expression of Th17-associated genes in melanoma patients treated with PD-1 blockade predicted poorer overall survival and response. Our study validates a triple combinatorial therapeutic strategy to overcome resistance to combined MEK inhibitor and PD-L1 blockade.

cancer biology↗