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Your search keyword '"Wickramasinghe P"' showing total 8 results
Start Over Author "Wickramasinghe P" Journal nature communications
8 results on '"Wickramasinghe P"'

3. Tumor-infiltrating mast cells are associated with resistance to anti-PD-1 therapy.

Author

Somasundaram, Rajasekharan, Connelly, Thomas, Choi, Robin, Choi, Hyeree, Samarkina, Anastasia, Li, Ling, Gregorio, Elizabeth, Chen, Yeqing, Thakur, Rohit, Abdel-Mohsen, Mohamed, Beqiri, Marilda, Kiernan, Meaghan, Perego, Michela, Wang, Fang, Xiao, Min, Brafford, Patricia, Yang, Xue, Xu, Xiaowei, Secreto, Anthony, Danet-Desnoyers, Gwenn, Traum, Daniel, Kaestner, Klaus H, Huang, Alexander C, Hristova, Denitsa, Wang, Joshua, Fukunaga-Kalabis, Mizuho, Krepler, Clemens, Ping-Chen, Fang, Zhou, Xiangyang, Gutierrez, Alexis, Rebecca, Vito W, Vonteddu, Prashanthi, Dotiwala, Farokh, Bala, Shashi, Majumdar, Sonali, Dweep, Harsh, Wickramasinghe, Jayamanna, Kossenkov, Andrew V, Reyes-Arbujas, Jorge, Santiago, Kenisha, Nguyen, Tran, Griss, Johannes, Keeney, Frederick, Hayden, James, Gavin, Brian J, Weiner, David, Montaner, Luis J, Liu, Qin, Peiffer, Lukas, Becker, Jürgen, Burton, Elizabeth M, Davies, Michael A, Tetzlaff, Michael T, Muthumani, Kar, Wargo, Jennifer A, Gabrilovich, Dmitry, and Herlyn, Meenhard

Subjects
B-Lymphocytes, T-Lymphocytes, Lymphocytes, Tumor-Infiltrating, Mast Cells, Animals, Mice, Transgenic, Humans, Melanoma, Drug Resistance, Neoplasm, Programmed Cell Death 1 Receptor, Sunitinib, Immune Checkpoint Inhibitors
Abstract

Anti-PD-1 therapy is used as a front-line treatment for many cancers, but mechanistic insight into this therapy resistance is still lacking. Here we generate a humanized (Hu)-mouse melanoma model by injecting fetal liver-derived CD34+ cells and implanting autologous thymus in immune-deficient NOD-scid IL2Rγnull (NSG) mice. Reconstituted Hu-mice are challenged with HLA-matched melanomas and treated with anti-PD-1, which results in restricted tumor growth but not complete regression. Tumor RNA-seq, multiplexed imaging and immunohistology staining show high expression of chemokines, as well as recruitment of FOXP3+ Treg and mast cells, in selective tumor regions. Reduced HLA-class I expression and CD8+/Granz B+ T cells homeostasis are observed in tumor regions where FOXP3+ Treg and mast cells co-localize, with such features associated with resistance to anti-PD-1 treatment. Combining anti-PD-1 with sunitinib or imatinib results in the depletion of mast cells and complete regression of tumors. Our results thus implicate mast cell depletion for improving the efficacy of anti-PD-1 therapy.

Published
2021

4. Observation of nanoscale opto-mechanical molecular damping as the origin of spectroscopic contrast in photo induced force microscopy.

Author

Almajhadi, Mohammad A, Uddin, Syed Mohammad Ashab, and Wickramasinghe, H Kumar

Subjects
physics.ins-det, physics.optics
Abstract

Infrared photoinduced force microscopy (IR-PiFM) is a scanning probe spectroscopic technique that maps sample morphology and chemical properties on the nanometer (nm)-scale. Fabricated samples with nm periodicity such as self-assembly of block copolymer films can be chemically characterized by IR-PiFM with relative ease. Despite the success of IR-PiFM, the origin of spectroscopic contrast remains unclear, preventing the scientific community from conducting quantitative measurements. Here we experimentally investigate the contrast mechanism of IR-PiFM for recording vibrational resonances. We show that the measured spectroscopic information of a sample is directly related to the energy lost in the oscillating cantilever, which is a direct consequence of a molecule excited at its vibrational optical resonance-coined as opto-mechanical damping. The quality factor of the cantilever and the local sample polarizability can be mathematically correlated, enabling quantitative analysis. The basic theory for dissipative tip-sample interactions is introduced to model the observed opto-mechanical damping.

Published
2020

5. Adaptive translational reprogramming of metabolism limits the response to targeted therapy in BRAFV600 melanoma

Author

Smith, Lorey K., Parmenter, Tiffany, Kleinschmidt, Margarete, Kusnadi, Eric P., Kang, Jian, Martin, Claire A., Lau, Peter, Patel, Riyaben, Lorent, Julie, Papadopoli, David, Trigos, Anna, Ward, Teresa, Rao, Aparna D., Lelliott, Emily J., Sheppard, Karen E., Goode, David, Hicks, Rodney J., Tiganis, Tony, Simpson, Kaylene J., Larsson, Ola, Blythe, Benjamin, Cullinane, Carleen, Wickramasinghe, Vihandha O., Pearson, Richard B., and McArthur, Grant A.

Published
2022
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