Fig. 8: Combined ERBB2 and anti-PD-1 blockade induces expansion of dominant T cell clones. | Nature Communications

Fig. 8: Combined ERBB2 and anti-PD-1 blockade induces expansion of dominant T cell clones.

From: ERBB2 signaling drives immune cell evasion and resistance against immunotherapy in small cell lung cancer

Fig. 8

Peripheral T cells of SCLC-bearing mice in treatment and healthy control were analyzed. a Clonotype distribution of all T cells in anti-PD-1 + ERBB2i-treated, vehicle-treated and healthy control mice (n = 1 per group). b Clonotype frequency of the top 10 clones in cytotoxic lymphocytes. The respective group is indicated by color code. c TCR clonality measured by inverted Shannon entropy. d Cluster analysis of TCR β-chain, calculated with quality method and global alignment using the Biostrings R package. e V- and J-gene usage in TCR β-chain of different treated mice. f UMAP of all T cells with cytotoxic (blue), TRBV14 & TRBVJ2-3 positive (red) and TRBV16 & TRBVJ2-7 positive (orange) T cells in ERBB2i + anti-PD-1 treated mice. g–i Comparison of the two most frequent cytotoxic clones in anti-PD-1 + ERBB2i (Clone 1 n = 67, Clone 2 n = 37) and vehicle (Clone 1 n = 6, Clone 2 n = 4) concerning GZMA, TIGIT, and TOX expression. The center lines represent the median or mean, box bounds represent Q1 and Q3 percentiles and whiskers extend to the minimum and maximum values. For Gzma: anti-PD-1 + ERBB2i Clone 1 Min = 0, Q1 = 2.931559, Mean = 3.719872, Median = 4.206237, Q3 = 4.630662, Max = 5.726883, Clone 2 Min = 0, Q1 = 3.631347, Mean = 3.920051, Median = 4.268613, Q3 = 4.739704, Max = 5.163969; Vehicle Clone 1 Min = 0, Mean = 0.4342388, Q3 = 1.163976, Max = 1.441456, Clone 2 Min = 3.544061, Mean = 4.172555, Median = 4.112799, Q3 = 4.599101, Max = 4.920561. For Tigit: anti-PD-1 + ERBB2i Clone 1 Min = 0, Mean = 0.02606225, Median = 0, Max = 1.746171; Vehicle Clone 1 Min = 0, Q1 = 1.322435, Mean = 1.572579, Median = 1.719329, Q3 = 2.029191, Max = 2.645192. For Tox: aPD-1 + ERBB2i Clone 2 Mean = 0.042270, Median = 0, Max = 1.563993. Vehicle Clone 1 Min = 0, Mean = 1.720013, Median = 1.720013, Q3 = 2.225449, Max = 2.654358. Statistical analysis was done using the two-sided Mann–Whitney test. *p  <  0.05, **p  <  0.01, ***p < 0.001. Source data are provided as a Source Data file.

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