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435. Huye LE, Nakazawa Y, Patel MP, Yvon E, Sun J, Savoldo B, et al. Combining mTor inhibitors with rapamycin-resistant T cells: a two-pronged approach to tumor elimination. Mol Ther. 2011;19(12):2239–48.

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437. Zheng W, O'Hear CE, Alli R, Basham JH, Abdelsamed HA, Palmer LE, et al. PI3K orchestration of the in vivo persistence of chimeric antigen receptor-modified T cells. Leukemia. 2018;32(5):1157–67.

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439. Funk CR, Wang S, Chen KZ, Waller A, Sharma A, Edgar CL, et al. PI3Kδ/γ inhibition promotes human CART cell epigenetic and metabolic reprogramming to enhance antitumor cytotoxicity. Blood. 2022;139(4):523–37.

440. Dwyer CJ, Arhontoulis DC, Rangel Rivera GO, Knochelmann HM, Smith AS, Wyatt MM, et al. Ex vivo blockade of PI3K gamma or delta signaling enhances the antitumor potency of adoptively transferred CD8. Eur J Immunol. 2020;50(9):1386–99.

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<figure><img src="image_15.png" /></figure>
424. Song M, Chen D, Lu B, Wang C, Zhang J, Huang L, et al. PTEN loss increases PD-L1 protein expression and affects the correlation between PD-L1 expression and clinical parameters in colorectal cancer. PLoS ONE. 2013;8(6):e65821.

425. O'Donnell JS, Massi D, Teng MWL, Mandala M. PI3K-AKT-mTOR inhibition in cancer immunotherapy, redux. Semin Cancer Biol. 2018;48:91–103.

426. Hirsch E, Ciraolo E, Franco I, Ghigo A, Martini M. PI3K in cancer-stroma interactions: bad in seed and ugly in soil. Oncogene. 2014;33(24):3083–90.

427. Peng W, Chen JQ, Liu C, Malu S, Creasy C, Tetzlaff MT, et al. Loss of PTEN Promotes Resistance to T Cell-Mediated Immunotherapy. Cancer Discov. 2016;6(2):202–16.

428. Yan C, Yang J, Saleh N, Chen SC, Ayers GD, Abramson VG, et al. Inhibition of the PI3K/mTOR Pathway in Breast Cancer to Enhance Response to Immune Checkpoint Inhibitors in Breast Cancer. Int J Mol Sci. 2021;22(10):5207.

429. Isoyama S, Mori S, Sugiyama D, Kojima Y, Tada Y, Shitara K, et al. Cancer immunotherapy with PI3K and PD-1 dual-blockade via optimal modulation of T cell activation signal. J Immunother Cancer. 2021;9(e002279).

430. Chandrasekaran S, Funk CR, Kleber T, Paulos CM, Shanmugam M, Waller EK. Strategies to Overcome Failures in T-Cell Immunotherapies by Targeting PI3K-δ and -γ. Front Immunol. 2021;12:718621.

431. Tawbi HA, Peng W, Phillips S, Milton DR, Amaria RN, Diab A, et al. Safety results from phase I/II study of the PI3Kβ inhibitor GSK2636771 (G) in combination with pembrolizumab (P) in patients (pts) with PD-1 refractory metastatic melanoma (MM) and PTEN loss. (Abstract). J Clin Oncol. 2020;38(15):e22000.

432. Jin J, Rohatgi A, Gabrielle A, Rose A, Wilson M, Bruno TC, et al. Interim results from a phase I/II study of duvelisib PI3Kδγ inhibitor and nivolumab in patients with advanced unresectable melanoma who have progressed on anti-PD1 therapy. (Abstract). J Clin Oncol. 2023;41(16):9540.

433. Bennani NN, Atherton P, Micallef I, Colgan JP, Thanarajasingam G, Nowakowski G, et al. A Phase II Study of Nivolumab in Patients with Relapsed or Refractory Peripheral T-Cell Lymphoma. Blood. 2019;134(624):467.

434. Shouse G, Siddiqi T, Popplewell LL, Muir A, Melgar I, Orand K, et al. A Phase I Trial of PI3Kαδ Inhibitor Copanlisib in Combination with Nivolumab in Patients with Richter's Transformation (RT) or Transformed Non-Hodgkin Lymphoma (tNHL). Blood. 2022;140:6633–4.

435. Huye LE, Nakazawa Y, Patel MP, Yvon E, Sun J, Savoldo B, et al. Combining mTor inhibitors with rapamycin-resistant T cells: a two-pronged approach to tumor elimination. Mol Ther. 2011;19(12):2239–48.

436. Stock S, Kluever AK, Endres S, Kobold S. Enhanced chimeric antigen receptor T cell therapy through co-application of synergistic combination partners. Biomedicines. 2022;10(2):307.

437. Zheng W, O'Hear CE, Alli R, Basham JH, Abdelsamed HA, Palmer LE, et al. PI3K orchestration of the in vivo persistence of chimeric antigen receptor-modified T cells. Leukemia. 2018;32(5):1157–67.

438. Stock S, Übelhart R, Schubert ML, Fan F, He B, Hoffmann JM, et al. Idelalisib for optimized CD19-specific chimeric antigen receptor T cells in chronic lymphocytic leukemia patients. Int J Cancer. 2019;145(5):1312–24.

439. Funk CR, Wang S, Chen KZ, Waller A, Sharma A, Edgar CL, et al. PI3Kδ/γ inhibition promotes human CART cell epigenetic and metabolic reprogramming to enhance antitumor cytotoxicity. Blood. 2022;139(4):523–37.

440. Dwyer CJ, Arhontoulis DC, Rangel Rivera GO, Knochelmann HM, Smith AS, Wyatt MM, et al. Ex vivo blockade of PI3K gamma or delta signaling enhances the antitumor potency of adoptively transferred CD8. Eur J Immunol. 2020;50(9):1386–99.

## Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Ready to submit your research? Choose BMC and benefit from:

* fast, convenient online submission

* thorough peer review by experienced researchers in your field

* rapid publication on acceptance

* support for research data, including large and complex data types

* gold Open Access which fosters wider collaboration and increased citations

* maximum visibility for your research: over 100M website views per year

At BMC, research is always in progress.

Learn more biomedcentral.com/submissions

<figure><img src="image_15.png" /></figure>