The patterns and kinetics of toxicity with anti–PD-1 agents are emerging. The incidence of grade 3 or above toxicities is low. We identify an idiosyncratic toxicity, eosinophilic fasciitis, that requires particular clinical vigilance to enable diagnosis and management.
Table of Contents
Cancer Immunology Miniatures
- Cancer Immunology MiniaturesJustine V. Cohen, Ahmed K. Alomari, Alexander O. Vortmeyer, Lucia B. Jilaveanu, Sarah B. Goldberg, Amit Mahajan, Veronica L. Chiang and Harriet M. KlugerCancer Immunol Res March 1 2016 4 (3) 179-182; DOI:10.1158/2326-6066.CIR-15-0160
This case report documents pseudoprogression in brain metastases treated with antibodies to PD-1. Use of immune checkpoint inhibitors in melanoma and other malignancies is increasing, making it important to recognize and treat effects unique to brain metastases.
- Research ArticlesRegulatory T Cells from Colon Cancer Patients Inhibit Effector T-cell Migration through an Adenosine-Dependent MechanismPatrik Sundström, Hanna Stenstad, Veronica Langenes, Filip Ahlmanner, Lisa Theander, Tapuka Gordon Ndah, Kamilla Fredin, Lars Börjesson, Bengt Gustavsson, Jérémy Bastid and Marianne Quiding-JärbrinkCancer Immunol Res March 1 2016 4 (3) 183-193; DOI:10.1158/2326-6066.CIR-15-0050
Regulatory T cells suppress many effector T-cell functions. Tregs from patients with colon cancer were found to inhibit transendothelial migration of conventional T cells, perhaps explaining the paucity of effector T cells within tumors.
- Research Articles | Free ArticleAntoni Ribas, Daniel Sanghoon Shin, Jesse Zaretsky, Juliet Frederiksen, Andrew Cornish, Earl Avramis, Elizabeth Seja, Christine Kivork, Janet Siebert, Paula Kaplan-Lefko, Xiaoyan Wang, Bartosz Chmielowski, John A. Glaspy, Paul C. Tumeh, Thinle Chodon, Dana Pe'er and Begoña Comin-AnduixCancer Immunol Res March 1 2016 4 (3) 194-203; DOI:10.1158/2326-6066.CIR-15-0210
Tumor biopsies from patients treated with antibodies to PD-1 showed that therapy altered tumor composition. T cells, B cells, and myeloid-derived suppressor cells were increased, and patients who responded to anti–PD-1 therapy had increased memory CD8+ T cells.
- Research ArticlesQiong J. Wang, Zhiya Yu, Kayla Griffith, Ken-ichi Hanada, Nicholas P. Restifo and James C. YangCancer Immunol Res March 1 2016 4 (3) 204-214; DOI:10.1158/2326-6066.CIR-15-0188
This study identifies HLA-A11*01–restricted T-cell receptors (TCRs) that specifically target mutated KRAS, which is an oncogenic driver mutation found in many types of cancers. These TCRs have antitumor activity and thus show potential for clinical use in multiple cancers.
- Research Articles | AuthorChoicePhase I Study of Random Healthy Donor–Derived Allogeneic Natural Killer Cell Therapy in Patients with Malignant Lymphoma or Advanced Solid TumorsYaewon Yang, Okjae Lim, Tae Min Kim, Yong-Oon Ahn, Hana Choi, Hyejin Chung, Bokyung Min, Jung Hyun Her, Sung Yoo Cho, Bhumsuk Keam, Se-Hoon Lee, Dong-Wan Kim, Yu Kyeong Hwang and Dae Seog HeoCancer Immunol Res March 1 2016 4 (3) 215-224; DOI:10.1158/2326-6066.CIR-15-0118
Completely allogeneic NK cells could provide a ready source of antitumor activity. This preliminary clinical trial shows that such cells are well tolerated and have potential benefits for cancer patients by upregulating the host immune responses against cancer.
- Research Articles | AuthorChoiceDarshil T. Jhaveri, Min-Sik Kim, Elizabeth D. Thompson, Lanqing Huang, Rajni Sharma, Alison P. Klein, Lei Zheng, Dung T. Le, Daniel A. Laheru, Akhilesh Pandey, Elizabeth M. Jaffee and Robert A. AndersCancer Immunol Res March 1 2016 4 (3) 225-233; DOI:10.1158/2326-6066.CIR-15-0200-T
Serum samples from patients in a phase II pancreas cancer vaccine clinical trial were subjected to quantitative proteomics. Three highly induced proteins in the pancreas after vaccination became targets of antibodies. Patients harboring these antibodies had improved clinical outcomes.
- Research ArticlesComprehensive Immune Profiling of Lung Adenocarcinomas Reveals Four Immunosubtypes with Plasma Cell Subtype a Negative IndicatorYutaka Kurebayashi, Katsura Emoto, Yuichiro Hayashi, Ikuo Kamiyama, Takashi Ohtsuka, Hisao Asamura and Michiie SakamotoCancer Immunol Res March 1 2016 4 (3) 234-247; DOI:10.1158/2326-6066.CIR-15-0214
Lung cancer is a complex disease with variable outcomes. Immune cells from 114 cases were quantified immunohistochemically, identifying four immunosubtypes of lung adenocarcinoma (CD8, mast cell, macrophage/DC, and plasma cell) that could potentially be useful for therapy selection.
- Research ArticlesImmunotherapy against Metastatic Melanoma with Human iPS Cell–Derived Myeloid Cell Lines Producing Type I InterferonsAzusa Miyashita, Satoshi Fukushima, Satoshi Nakahara, Yosuke Kubo, Aki Tokuzumi, Junji Yamashita, Jun Aoi, Miwa Haruta, Satoru Senju, Yasuharu Nishimura, Masatoshi Jinnin and Hironobu IhnCancer Immunol Res March 1 2016 4 (3) 248-258; DOI:10.1158/2326-6066.CIR-15-0096
Human myeloid cell lines derived from iPS cells were genetically modified to express type I IFNs. These cells durably inhibited the growth of human melanoma in xenograft models by infiltrating tumors and providing local antitumor effects.
- Research ArticlesSatoshi Shiina, Masasuke Ohno, Fumiharu Ohka, Shunichiro Kuramitsu, Akane Yamamichi, Akira Kato, Kazuya Motomura, Kuniaki Tanahashi, Takashi Yamamoto, Reiko Watanabe, Ichiro Ito, Takeshi Senga, Michinari Hamaguchi, Toshihiko Wakabayashi, Mika K. Kaneko, Yukinari Kato, Vidyalakshmi Chandramohan, Darell D. Bigner and Atsushi NatsumeCancer Immunol Res March 1 2016 4 (3) 259-268; DOI:10.1158/2326-6066.CIR-15-0060
The glioblastoma subtypes with the worst prognoses often bear podoplanin. T cells expressing a chimeric antigen receptor that targets podoplanin were specific and effective against PDPN-positive glioblastoma cells in vitro and increased survival time in a mouse model.